Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Drug Targets
  4. Volume 25, Issue 15
  5. Article
Volume 25, Issue 15
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that impacts a significant portion of the population. Despite extensive research, an effective cure for PD remains elusive, and conventional pharmacological treatments often face limitations in efficacy and management of symptoms. There has been a lot of discussion about using nanotechnology to increase the bioavailability of small- molecule drugs to target cells in recent years. It is possible that PD treatment might become far more effective and have fewer side effects if medication delivery mechanisms were to be improved. Potential alternatives to pharmacological therapy for molecular imaging and treatment of PD may lie in abnormal proteins such as parkin, α-synuclein, leucine-rich repeat serine and threonine protein kinase 2. Published research has demonstrated encouraging outcomes when nanomedicine-based approaches are used to address the challenges of PD therapy. So, to address the present difficulties of antiparkinsonian treatment, this review outlines the key issues and limitations of antiparkinsonian medications, new therapeutic strategies, and the breadth of delivery based on nanomedicine. This review covers a wide range of subjects, including drug distribution in the brain, the efficacy of drug-loaded nano-carriers in crossing the blood-brain barrier, and their release profiles. In PD, the nano-carriers are also used. Novel techniques of pharmaceutical delivery are currently made possible by vesicular carriers, which eliminate the requirement to cross the blood-brain barrier (BBB).

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdt/10.2174/0113894501312703240826070530
2024-09-11
2024-11-22

  • From This Site

    /content/journals/cdt/10.2174/0113894501312703240826070530
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SafiriS. NooriM. NejadghaderiS.A. MousaviS.E. SullmanM.J.M. Araj-KhodaeiM. SinghK. KolahiA.A. GharagozliK. The burden of Parkinson’s disease in the Middle East and North Africa region, 1990–2019: results from the global burden of disease study 2019.BMC Public Health202323110710.1186/s12889‑023‑15018‑x36642724
     [Google Scholar]
  2. AarslandD. BatzuL. HallidayG.M. GeurtsenG.J. BallardC. Ray ChaudhuriK. WeintraubD. Parkinson disease-associated cognitive impairment.Nat. Rev. Dis. Primers2021714710.1038/s41572‑021‑00280‑334210995
     [Google Scholar]
  3. YangJ. IdowuA. RosenthalL. MaoX. Parkinson’s disease fluid biomarkers for differential diagnosis of atypical parkinsonian syndromes.Clin. Transl. Discov.202331e15010.1002/ctd2.150
     [Google Scholar]
  4. RameshS. ArachchigeA.S.P.M. Depletion of dopamine in Parkinson’s disease and relevant therapeutic options: A review of the literature.AIMS Neurosci.202310320023110.3934/Neuroscience.202301737841347
     [Google Scholar]
  5. DauerW. PrzedborskiS. Parkinson’s Disease.Neuron200339688990910.1016/S0896‑6273(03)00568‑312971891
     [Google Scholar]
  6. SivanandyP. LeeyT.C. XiangT.C. LingT.C. Wey HanS.A. SemilanS.L.A. HongP.K. Systematic Review on Parkinson’s Disease Medications, Emphasizing on Three Recently Approved Drugs to Control Parkinson’s Symptoms.Int. J. Environ. Res. Public Health202119136410.3390/ijerph1901036435010624
     [Google Scholar]
  7. AhmadJ. HaiderN. KhanM.A. MdS. AlhakamyN.A. GhoneimM.M. AlshehriS. Sarim ImamS. AhmadM.Z. MishraA. Novel therapeutic interventions for combating Parkinson’s disease and prospects of Nose-to-Brain drug delivery.Biochem. Pharmacol.202219511484910.1016/j.bcp.2021.11484934808125
     [Google Scholar]
  8. PatelV. ChavdaV. ShahJ. Nanotherapeutics in Neuropathologies: Obstacles, Challenges and Recent Advancements in CNS Targeted Drug Delivery Systems.Curr. Neuropharmacol.202119569371010.2174/1570159X1866620080714352632851949
     [Google Scholar]
  9. NiaziS.K. Non-Invasive Drug Delivery across the Blood–Brain Barrier: A Prospective Analysis.Pharmaceutics20231511259910.3390/pharmaceutics1511259938004577
     [Google Scholar]
  10. WuD. ChenQ. ChenX. HanF. ChenZ. WangY. The blood–brain barrier: structure, regulation, and drug delivery.Signal Transduct. Target. Ther.20238121710.1038/s41392‑023‑01481‑w37231000
     [Google Scholar]
  11. ZhangS. GanL. CaoF. WangH. GongP. MaC. RenL. LinY. LinX. The barrier and interface mechanisms of the brain barrier, and brain drug delivery.Brain Res. Bull.2022190698310.1016/j.brainresbull.2022.09.01736162603
     [Google Scholar]
  12. ZhaoC. ZhuX. TanJ. MeiC. CaiX. KongF. Lipid-based nanoparticles to address the limitations of GBM therapy by overcoming the blood-brain barrier, targeting glioblastoma stem cells, and counteracting the immunosuppressive tumor microenvironment.Biomed. Pharmacother.202417111611310.1016/j.biopha.2023.11611338181717
     [Google Scholar]
  13. AdamH. GopinathSCB. ArshadMK. AdamT. ParminNA. HuseinI An update on pathogenesis and clinical scenario for Parkinson ’ s disease : diagnosis and treatment.3 Biotech2023135118
     [Google Scholar]
  14. De MartiniL.B. SulmonaC. BrambillaL. RossiD. Cell-penetrating peptides as valuable tools for nose-to-brain delivery of biological drugs.Cells20231212164310.3390/cells1212164337371113
     [Google Scholar]
  15. AyubA. WettigS. An overview of nanotechnologies for drug delivery to the brain.Pharmaceutics202214222410.3390/pharmaceutics1402022435213957
     [Google Scholar]
  16. WuD.D. SalahY.A. NgowiE.E. ZhangY.X. KhattakS. KhanN.H. WangY. LiT. GuoZ.H. WangY.M. JiX.Y. Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration.iScience202326810732110.1016/j.isci.2023.10732137554468
     [Google Scholar]
  17. ShabaniL. AbbasiM. AzarnewZ. AmaniA.M. VaezA. Neuro-nanotechnology: diagnostic and therapeutic nano-based strategies in applied neuroscience.Biomed. Eng. Online2023221110.1186/s12938‑022‑01062‑y36593487
     [Google Scholar]
  18. MustafaG. HassanD. ZeeshanM. Ruiz-PulidoG. EbrahimiN. MobasharA. PourmadadiM. RahdarA. SargaziS. Fathi-karkanS. MedinaD.I. Díez-PascualA.M. Advances in nanotechnology versus stem cell therapy for the theranostics of Huntington’s disease.J. Drug Deliv. Sci. Technol.202387104774[Internet].10.1016/j.jddst.2023.104774
     [Google Scholar]
  19. YusufA. AlmotairyA.R.Z. HenidiH. AlshehriO.Y. AldughaimM.S. Nanoparticles as Drug Delivery Systems: A Review of the Implication of Nanoparticles’ Physicochemical Properties on Responses in Biological Systems.Polymers (Basel)2023157159610.3390/polym1507159637050210
     [Google Scholar]
  20. ChehelgerdiM. ChehelgerdiM. AllelaO.Q.B. PechoR.D.C. JayasankarN. RaoD.P. ThamaraikaniT. VasanthanM. ViktorP. LakshmaiyaN. SaadhM.J. AmajdA. Abo-ZaidM.A. Castillo-AcoboR.Y. IsmailA.H. AminA.H. Akhavan-SigariR. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation.Mol. Cancer202322116910.1186/s12943‑023‑01865‑037814270
     [Google Scholar]
  21. ArtusiC.A. SarroL. ImbalzanoG. FabbriM. LopianoL. Safety and efficacy of tolcapone in Parkinson’s disease: systematic review.Eur. J. Clin. Pharmacol.202177681782910.1007/s00228‑020‑03081‑x33415500
     [Google Scholar]
  22. EttchetoM. BusquetsO. Sánchez-LopezE. CanoA. ManzineP.R. VerdaguerE. OlloquequiJ. AuladellC. FolchJ. CaminsA. The preclinical discovery and development of opicapone for the treatment of Parkinson’s disease.Expert Opin. Drug Discov.2020159993100310.1080/17460441.2020.176758032450711
     [Google Scholar]
  23. HawthorneG.H. BernuciM.P. BortolanzaM. TumasV. IssyA.C. Del-BelE. Nanomedicine to overcome current Parkinson’s treatment liabilities: A systematic review.Neurotox. Res.201630471572910.1007/s12640‑016‑9663‑z27581037
     [Google Scholar]
  24. ItinC. KomargodskiR. BaraschD. DombA.J. HoffmanA. prolonged delivery of apomorphine through the buccal mucosa, towards a noninvasive sustained administration method in Parkinson’s disease: in vivo investigations in pigs.J. Pharm. Sci.202111041824183310.1016/j.xphs.2020.12.01033333142
     [Google Scholar]
  25. KulkarniA.D. VanjariY.H. SanchetiK.H. BelgamwarV.S. SuranaS.J. PardeshiC.V. Nanotechnology-mediated nose to brain drug delivery for Parkinson’s disease: a mini review.J. Drug Target.201523977578810.3109/1061186X.2015.102080925758751
     [Google Scholar]
  26. KhatriD.K. PreetiK. TonapeS. BhattacharjeeS. PatelM. ShahS. SinghP.K. SrivastavaS. GugulothuD. VoraL. SinghS.B. Nanotechnological advances for nose to brain delivery of therapeutics to improve the Parkinson therapy.Curr. Neuropharmacol.202321349351610.2174/1570159X2066622050702270135524671
     [Google Scholar]
  27. GursoyA. Nanofarmasötikler ve Uygulamaları. NanopartiküllerB.E. IstanbulKontrollü Salım Sistemleri Derneği20142340
     [Google Scholar]
  28. ModiG. PillayV. ChoonaraY.E. Advances in the treatment of neurodegenerative disorders employing nanotechnology.Ann. N. Y. Acad. Sci.20101184115417210.1111/j.1749‑6632.2009.05108.x20146696
     [Google Scholar]
  29. KostarelosK. MillerA.D. Synthetic, self-assembly ABCD nanoparticles; a structural paradigm for viable synthetic non-viral vectors.Chem. Soc. Rev.2005341197099410.1039/b307062j16239997
     [Google Scholar]
  30. FogedC. NielsenH.M. Cell-penetrating peptides for drug delivery across membrane barriers.Expert Opin. Drug Deliv.20085110511710.1517/17425247.5.1.10518095931
     [Google Scholar]
  31. GielenM.E.R. Metallotherapeutic drugs and metal-based diagnostic agents: The use of metals in medicineEnglandJohn Wiley and Sons Ltd200510.1002/0470864052
     [Google Scholar]
  32. IqbalA. AhmadI. KhalidM.H. NawazM.S. GanS.H. KamalM.A. Nanoneurotoxicity to nanoneuroprotection using biological and computational approaches.J. Environ. Sci. Health Part C Environ. Carcinog. Ecotoxicol. Rev.201331325628410.1080/10590501.2013.82970624024521
     [Google Scholar]
  33. AllenT.M. CullisP.R. Drug delivery systems: entering the mainstream.Science200430356651818182210.1126/science.109583315031496
     [Google Scholar]
  34. FarokhzadO.C. LangerR. Impact of nanotechnology on drug delivery.ACS Nano200931162010.1021/nn900002m19206243
     [Google Scholar]
  35. WohlfartS. GelperinaS. KreuterJ. Transport of drugs across the blood–brain barrier by nanoparticles.J. Control. Release2012161226427310.1016/j.jconrel.2011.08.01721872624
     [Google Scholar]
  36. HaddadF. SawalhaM. KhawajaY. NajjarA. KaramanR. Dopamine and levodopa prodrugs for the treatment of Parkinson’sdisease.Molecules20172314010.3390/molecules2301004029295587
     [Google Scholar]
  37. ShinM. KimH.K. LeeH. Dopamine-loaded poly(d,l-lactic-co-glycolic acid) microspheres: New strategy for encapsulating small hydrophilic drugs with high efficiency.Biotechnol. Prog.201430121522310.1002/btpr.183524281843
     [Google Scholar]
  38. PahujaR. SethK. ShuklaA. ShuklaR.K. BhatnagarP. ChauhanL.K.S. SaxenaP.N. ArunJ. ChaudhariB.P. PatelD.K. SinghS.P. ShuklaR. KhannaV.K. KumarP. ChaturvediR.K. GuptaK.C. Trans-blood brain barrier delivery of dopamine-loaded nanoparticles reverses functional deficits in parkinsonian rats.ACS Nano2015954850487110.1021/nn506408v25825926
     [Google Scholar]
  39. Monge-FuentesV. Biolchi MayerA. LimaM.R. GeraldesL.R. ZanottoL.N. MoreiraK.G. MartinsO.P. PivaH.L. FelipeM.S.S. AmaralA.C. BoccaA.L. TedescoA.C. MortariM.R. Dopamine-loaded nanoparticle systems circumvent the blood–brain barrier restoring motor function in mouse model for Parkinson’s Disease.Sci. Rep.20211111518510.1038/s41598‑021‑94175‑834312413
     [Google Scholar]
  40. BiC. WangA. ChuY. LiuS. MuH. LiuW. WuZ. SunK. LiY. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment.Int. J. Nanomedicine2016116547655910.2147/IJN.S12093927994458
     [Google Scholar]
  41. SridharV. GaudR. BajajA. WairkarS. Pharmacokinetics and pharmacodynamics of intranasally administered selegiline nanoparticles with improved brain delivery in Parkinson’s disease.Nanomedicine20181482609261810.1016/j.nano.2018.08.00430171904
     [Google Scholar]
  42. SharmaS. LohanS. MurthyR.S.R. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery.Drug Dev. Ind. Pharm.201440786987810.3109/03639045.2013.78905123600649
     [Google Scholar]
  43. BaliN.R. SalveP.S. Impact of rasagiline nanoparticles on brain targeting efficiency via gellan gum based transdermal patch: A nanotheranostic perspective for Parkinsonism.Int. J. Biol. Macromol.20201641006102410.1016/j.ijbiomac.2020.06.26132619667
     [Google Scholar]
  44. BaliN.R. SalveP.S. Selegiline nanoparticle embedded transdermal film: An alternative approach for brain targeting in Parkinson’s disease.J. Drug Deliv. Sci. Technol.201954101299[CrossRef].10.1016/j.jddst.2019.101299
     [Google Scholar]
  45. YangX. ZhengR. CaiY. LiaoM. YuanW. LiuZ. Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats.Int. J. Nanomedicine2012720772086[CrossRef].22619544
     [Google Scholar]
  46. RajR. WairkarS. SridharV. GaudR. Pramipexole dihydrochloride loaded chitosan nanoparticles for nose to brain delivery: Development, characterization and in vivo anti-Parkinson activity.Int. J. Biol. Macromol.2018109273510.1016/j.ijbiomac.2017.12.05629247729
     [Google Scholar]
  47. MengX.Y. HuangA.Q. KhanA. ZhangL. SunX.Q. SongH. HanJ. SunQ.R. WangY.D. LiX.L. Vascular endothelial growth factor-loaded poly-lactic-co-glycolic acid nanoparticles with controlled release protect the dopaminergic neurons in Parkinson’s rats.Chem. Biol. Drug Des.202095663163910.1111/cbdd.1368132167672
     [Google Scholar]
  48. PillayS. PillayV. ChoonaraY.E. NaidooD. KhanR.A. du ToitL.C. NdesendoV.M.K. ModiG. DanckwertsM.P. IyukeS.E. Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain.Int. J. Pharm.20093821-227729010.1016/j.ijpharm.2009.08.02119703530
     [Google Scholar]
  49. RayS. SinhaP. LahaB. MaitiS. BhattacharyyaU.K. NayakA.K. Polysorbate 80 coated crosslinked chitosan nanoparticles of ropinirole hydrochloride for brain targeting.J. Drug Deliv. Sci. Technol.2018482129[CrossRef].10.1016/j.jddst.2018.08.016
     [Google Scholar]
  50. Sudhir DhoteN. Dineshbhai PatelR. KuwarU. AgrawalM. AlexanderA. JainP. Application of Thermoresponsive Smart Polymers based in situ Gel as a Novel Carrier for Tumor Targeting [Internet]. Vol. 24.Curr. Cancer Drug Targets2024122
     [Google Scholar]
  51. BhairamM. PrasadJ. VermaK. JainP. GidwaniB. Formulation of transdermal patch of Losartan Potassium & Glipizide for the treatment of hypertension & diabetes.Mater. Today Proc.2023835968[Internet].10.1016/j.matpr.2023.01.147
     [Google Scholar]
  52. PatelR. KuwarU. DhoteN. AlexanderA. NakhateK. JainP. Ajazuddin Natural Polymers as a Carrier for the Effective Delivery of Antineoplastic Drugs.Curr. Drug Deliv.202421219321010.2174/156720182066623011217003536644864
     [Google Scholar]
  53. JainA. JainP. SoniP. TiwariA. TiwariS.P. Design and Characterization of Silver Nanoparticles of Different Species of Curcuma in the Treatment of Cancer Using Human Colon Cancer Cell Line (HT-29).J. Gastrointest. Cancer2023541909510.1007/s12029‑021‑00788‑735043370
     [Google Scholar]
  54. IslamM. HuangY. JainP. FanB. TongL. WangF. Enzymatic hydrolysis of soy protein to high moisture textured meat analogue with emphasis on antioxidant effects: As a tool to improve techno-functional property.Biocatal. Agric. Biotechnol.202350102700[Internet].10.1016/j.bcab.2023.102700
     [Google Scholar]
  55. AnY. TangL. JiangX. ChenH. YangM. JinL. ZhangS. WangC. ZhangW. A photoelectrochemical immunosensor based on Au-doped TiO2 nanotube arrays for the detection of α-synuclein.Chemistry20101648144391444610.1002/chem.20100165421038326
     [Google Scholar]
  56. DuanY. DharA. PatelC. KhimaniM. NeogiS. SharmaP. Siva KumarN. VekariyaR.L. A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems.RSC Advances20201045267772679110.1039/D0RA03491F35515778
     [Google Scholar]
  57. CorreiaA.C. MonteiroA.R. SilvaR. MoreiraJ.N. Sousa LoboJ.M. SilvaA.C. Lipid nanoparticles strategies to modify pharmacokinetics of central nervous system targeting drugs: Crossing or circumventing the blood–brain barrier (BBB) to manage neurological disorders.Adv. Drug Deliv. Rev.202218911448510.1016/j.addr.2022.11448535970274
     [Google Scholar]
  58. DiwanR. RaviP.R. PathareN.S. AggarwalV. Pharmacodynamic, pharmacokinetic and physical characterization of cilnidipine loaded solid lipid nanoparticles for oral delivery optimized using the principles of design of experiments.Colloids Surf. B Biointerfaces202019311107310.1016/j.colsurfb.2020.11107332388122
     [Google Scholar]
  59. LeeD. MinkoT. Nanotherapeutics for nose-to-brain drug delivery: An approach to bypass the blood brain barrier.Pharmaceutics20211312204910.3390/pharmaceutics1312204934959331
     [Google Scholar]
  60. TsaiM.J. HuangY.B. WuP.C. FuY.S. KaoY.R. FangJ.Y. TsaiY.H. Oral apomorphine delivery from solid lipid nanoparticles with different monostearate emulsifiers: pharmacokinetic and behavioral evaluations.J. Pharm. Sci.2011100254755710.1002/jps.2228520740670
     [Google Scholar]
  61. UppuluriC.T. RaviP.R. DalviA.V. Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease.Int. J. Pharm.202160612088110.1016/j.ijpharm.2021.12088134273426
     [Google Scholar]
  62. DudhipalaN. GorreT. Neuroprotective effect of ropinirole lipid nanoparticles enriched hydrogel for parkinson's disease: in vitro, ex-vivo, pharmacokinetic and pharmacodynamic evaluation.Pharmaceutics.202012544810.3390/pharmaceutics12050448.32414195
     [Google Scholar]
  63. PardeshiC.V. BelgamwarV.S. Improved brain pharmacokinetics following intranasal administration of N,N,N -trimethyl chitosan tailored mucoadhesive NLCs.Mater. Technol.2020355249266[CrossRef].10.1080/10667857.2019.1674522
     [Google Scholar]
  64. CalvoP. GouritinB. ChacunH. DesmaëleD. D’AngeloJ. NoelJ.P. GeorginD. FattalE. AndreuxJ.P. CouvreurP. Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery.Pharm. Res.20011881157116610.1023/A:101093112774511587488
     [Google Scholar]
  65. AlqahtaniM.S. KaziM. AlsenaidyM.A. AhmadM.Z. Advances in oral drug delivery.Front. Pharmacol.20211261841110.3389/fphar.2021.61841133679401
     [Google Scholar]
  66. AzmanM. SabriA.H. AnjaniQ.K. MustaffaM.F. HamidK.A. Intestinal absorption study: Challenges and absorption enhancement strategies in improving oral drug delivery.Pharmaceuticals (Basel)202215897510.3390/ph1508097536015123
     [Google Scholar]
  67. WangY. BurgessD.J. Microsphere technologies.Long Acting Injections and Implants. JeremyC.W. DianeJ.B. New York, NY, USASpringer201216719410.1007/978‑1‑4614‑0554‑2_10
     [Google Scholar]
  68. UhrichK.E. CannizzaroS.M. LangerR.S. ShakesheffK.M. Polymeric systems for controlled drug release.Chem. Rev.199999113181319810.1021/cr940351u11749514
     [Google Scholar]
  69. JainR. ShahN.H. MalickA.W. RhodesC.T. Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches.Drug Dev. Ind. Pharm.199824870372710.3109/036390498090827199876519
     [Google Scholar]
  70. AbadiS.S.H. MoinA. VeerabhadrappaG.H. Fabricated microparticles: An innovative method to minimize the side effects of NSAIDs in arthritis.Crit. Rev. Ther. Drug Carrier Syst.201633543348810.1615/CritRevTherDrugCarrierSyst.201601662427910742
     [Google Scholar]
  71. TranV.T. BenoîtJ.P. Venier-JulienneM.C. Why and how to prepare biodegradable, monodispersed, polymeric microparticles in the field of pharmacy?Int. J. Pharm.20114071-211110.1016/j.ijpharm.2011.01.02721256947
     [Google Scholar]
  72. SuY. LiuJ. TanS. LiuW. WangR. ChenC. PLGA sustained-release microspheres loaded with an insoluble small-molecule drug: microfluidic-based preparation, optimization, characterization, and evaluation in vitro and in vivo .Drug Deliv.20222911437144610.1080/10717544.2022.207241335532150
     [Google Scholar]
  73. SuY. ZhangB. SunR. LiuW. ZhuQ. ZhangX. WangR. ChenC. PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application.Drug Deliv.20212811397141810.1080/10717544.2021.193875634184949
     [Google Scholar]
  74. O’BrienM.N. JiangW. WangY. LoffredoD.M. Challenges and opportunities in the development of complex generic long-acting injectable drug products.J. Control. Release202133614415810.1016/j.jconrel.2021.06.01734126170
     [Google Scholar]
  75. SharifiF. OtteA. YoonG. ParkK. Continuous in-line homogenization process for scale-up production of naltrexone-loaded PLGA microparticles.J. Control. Release202032534735810.1016/j.jconrel.2020.06.02332645336
     [Google Scholar]
  76. ChereddyK.K. VandermeulenG. PréatV. PLGA based drug delivery systems: Promising carriers for wound healing activity.Wound Repair Regen.201624222323610.1111/wrr.1240426749322
     [Google Scholar]
  77. FreitasS. MerkleH.P. GanderB. Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology.J. Control. Release2005102231333210.1016/j.jconrel.2004.10.01515653154
     [Google Scholar]
  78. LeeJ. KwonH.J. JiH. ChoS.H. ChoE.H. HanH.D. ShinB.C. Marbofloxacin-encapsulated microparticles provide sustained drug release for treatment of veterinary diseases.Mater. Sci. Eng. C20166051151710.1016/j.msec.2015.12.00426706558
     [Google Scholar]
  79. RamazaniF. ChenW. van NostrumC.F. StormG. KiesslingF. LammersT. HenninkW.E. KokR.J. Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: State-of-the-art and challenges.Int. J. Pharm.20164991-235836710.1016/j.ijpharm.2016.01.02026795193
     [Google Scholar]
  80. ShiY. LiL. Current advances in sustained-release systems for parenteral drug delivery.Expert Opin. Drug Deliv.2005261039105810.1517/17425247.2.6.103916296808
     [Google Scholar]
  81. van de WeertM. HenninkW.E. JiskootW. Protein instability in poly(lactic-co-glycolic acid) microparticles.Pharm. Res.200017101159116710.1023/A:102649820987411145219
     [Google Scholar]
  82. WissingT.B. BonitoV. van HaaftenE.E. van DoeselaarM. BrugmansM.M.C.P. JanssenH.M. BoutenC.V.C. SmitsA.I.P.M. Macrophagedriven biomaterial degradation depends on scaffold microarchitecture.Front. Bioeng. Biotechnol.201978710.3389/fbioe.2019.0008731080796
     [Google Scholar]
  83. FogedC. BrodinB. FrokjaerS. SundbladA. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model.Int. J. Pharm.2005298231532210.1016/j.ijpharm.2005.03.03515961266
     [Google Scholar]
  84. SinhaV.R. TrehanA. Biodegradable microspheres for protein delivery.J. Control. Release200390326128010.1016/S0168‑3659(03)00194‑912880694
     [Google Scholar]
  85. GasmiH. SiepmannF. HamoudiM.C. DanedeF. VerinJ. WillartJ.F. SiepmannJ. Towards a better understanding of the different release phases from PLGA microparticles: Dexamethasone-loaded systems.Int. J. Pharm.2016514118919910.1016/j.ijpharm.2016.08.03227543353
     [Google Scholar]
  86. TamaniF. BassandC. HamoudiM.C. SiepmannF. SiepmannJ. Mechanistic explanation of the (up to) 3 release phases of PLGA microparticles: Monolithic dispersions studied at lower temperatures.Int. J. Pharm.202159612022010.1016/j.ijpharm.2021.12022033486018
     [Google Scholar]
  87. ShiZ. FanZ. ZhangH. LiS. YuanH. TongJ. Localized delivery of brain-derived neurotrophic factor from PLGA microspheres promotes peripheral nerve regeneration in rats.J. Orthop. Surg. Res.202217117210.1186/s13018‑022‑02985‑x35303915
     [Google Scholar]
  88. HerránE. Ruiz-OrtegaJ.Á. AristietaA. IgartuaM. RequejoC. LafuenteJ.V. UgedoL. PedrazJ.L. HernándezR.M. in vivo administration of VEGF- and GDNF-releasing biodegradable polymeric microspheres in a severe lesion model of Parkinson’s disease.Eur. J. Pharm. Biopharm.20138531183119010.1016/j.ejpb.2013.03.03423639739
     [Google Scholar]
  89. LiS. LiuJ. LiG. ZhangX. XuF. FuZ. TengL. LiY. SunF. Near-infrared light-responsive, pramipexole-loaded biodegradable PLGA microspheres for therapeutic use in Parkinson’s disease.Eur. J. Pharm. Biopharm.201914111110.1016/j.ejpb.2019.05.01331100429
     [Google Scholar]
  90. KanwarN. BhandariR. KuhadA. SinhaV.R. Polycaprolactone-based neurotherapeutic delivery of rasagiline targeting behavioral and biochemical deficits in Parkinson’s disease.Drug Deliv. Transl. Res.20199589190510.1007/s13346‑019‑00625‑230877626
     [Google Scholar]
  91. AgbayA. MohtaramN.K. WillerthS.M. Controlled release of glial cell line-derived neurotrophic factor from poly(ε-caprolactone) microspheres.Drug Deliv. Transl. Res.20144215917010.1007/s13346‑013‑0189‑025786730
     [Google Scholar]
  92. ParthipanA.K. GuptaN. PandeyK. SharmaB. JacobJ. SahaS. One-step fabrication of bicompartmental microparticles as a dual drug delivery system for Parkinson’s disease management.J. Mater. Sci.201954173074410.1007/s10853‑018‑2819‑x
     [Google Scholar]
  93. KashifP.M. MadniA. AshfaqM. RehmanM. MahmoodM.A. KhanM.I. TahirN. Development of eudragit RS 100 microparticles loaded with ropinirole: Optimization and in vitro evaluation studies.AAPS PharmSciTech20171851810182210.1208/s12249‑016‑0653‑527830514
     [Google Scholar]
  94. GarbayoE. AnsorenaE. LanaH. Carmona-AbellanM.M. MarcillaI. LanciegoJ.L. LuquinM.R. Blanco-PrietoM.J. Brain delivery of microencapsulated GDNF induces functional and structural recovery in parkinsonian monkeys.Biomaterials2016110112310.1016/j.biomaterials.2016.09.01527697668
     [Google Scholar]
  95. FernándezM. NegroS. SlowingK. Fernández-CarballidoA. BarciaE. An effective novel delivery strategy of rasagiline for Parkinson’s disease.Int. J. Pharm.20114191-227128010.1016/j.ijpharm.2011.07.02921807080
     [Google Scholar]
  96. FabbriM. BarbosaR. RascolO. Off-time treatment options for Parkinson’s disease.Neurol. Ther.202312239142410.1007/s40120‑022‑00435‑836633762
     [Google Scholar]
  97. D’AurizioE. van NostrumC.F. van SteenbergenM.J. SozioP. SiepmannF. SiepmannJ. HenninkW.E. Di StefanoA. Preparation and characterization of poly(lactic-co-glycolic acid) microspheres loaded with a labile antiparkinson prodrug.Int. J. Pharm.20114091-228929610.1016/j.ijpharm.2011.02.03621356295
     [Google Scholar]
  98. D’AurizioE. SozioP. CerasaL.S. VaccaM. BrunettiL. OrlandoG. ChiavaroliA. KokR.J. HenninkW.E. Di StefanoA. Biodegradable microspheres loaded with an anti-Parkinson prodrug: an in vivo pharmacokinetic study.Mol. Pharm.2011862408241510.1021/mp200337h22014118
     [Google Scholar]
  99. SubramaniT. GanapathyswamyH. An overview of liposomal nano-encapsulation techniques and its applications in food and nutraceutical.J. Food Sci. Technol.202057103545355510.1007/s13197‑020‑04360‑232903987
     [Google Scholar]
  100. ShiY. LuA. WangX. BelhadjZ. WangJ. ZhangQ. A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives.Acta Pharm. Sin. B20211182396241510.1016/j.apsb.2021.05.00234522592
     [Google Scholar]
  101. Grassin-DelyleS. BuenestadoA. NalineE. FaisyC. Blouquit-LayeS. CoudercL.J. Le GuenM. FischlerM. DevillierP. Intranasal drug delivery: An efficient and non-invasive route for systemic administration.Pharmacol. Ther.2012134336637910.1016/j.pharmthera.2012.03.00322465159
     [Google Scholar]
  102. MiglioreM.M. OrtizR. DyeS. CampbellR.B. AmijiM.M. WaszczakB.L. Neurotrophic and neuroprotective efficacy of intranasal GDNF in a rat model of Parkinson’s disease.Neuroscience2014274112310.1016/j.neuroscience.2014.05.01924845869
     [Google Scholar]
  103. XiangY. WuQ. LiangL. WangX. WangJ. ZhangX. PuX. ZhangQ. Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting delivery against the Parkinson’s disease in the MPTP-induced mice model.J. Drug Target.2012201677510.3109/1061186X.2011.59549022149216
     [Google Scholar]
  104. TrivediR. UmekarM. KotagaleN. BondeS. TaksandeJ. Design, evaluation and in vivo pharmacokinetic study of a cationic flexible liposomes for enhanced transdermal delivery of pramipexole.J. Drug Deliv. Sci. Technol.20216110231310.1016/j.jddst.2020.102313
     [Google Scholar]
  105. BjörklundA. DunnettS.B. Dopamine neuron systems in the brain: an update.Trends Neurosci.200730519420210.1016/j.tins.2007.03.00617408759
     [Google Scholar]
  106. CassanoT. LopalcoA. de CandiaM. LaquintanaV. LopedotaA. CutrignelliA. PerroneM. IacobazziR.M. BedseG. FrancoM. DenoraN. AltomareC.D. Oxazepam-dopamine conjugates increase dopamine delivery into striatum of intact rats.Mol. Pharm.20171493178318710.1021/acs.molpharmaceut.7b0040528780872
     [Google Scholar]
  107. DenoraN. CassanoT. LaquintanaV. LopalcoA. TrapaniA. CimminoC.S. LaconcaL. GiuffridaA. TrapaniG. Novel codrugs with GABAergic activity for dopamine delivery in the brain.Int. J. Pharm.20124371-222123110.1016/j.ijpharm.2012.08.02322940209
     [Google Scholar]
  108. LopalcoA. CutrignelliA. DenoraN. LopedotaA. FrancoM. LaquintanaV. Transferrin functionalized liposomes loading dopamine HCl: Development and permeability studies across an in vitro model of human blood-brain barrier.Nanomaterials (Basel)20188317810.3390/nano803017829558440
     [Google Scholar]
  109. RekhaM.R. SharmaP. Nanoparticle Mediated Oral Delivery of Peptides and Proteins: Challenges and Perspectives.Peptide and Protein Delivery.London, UKElsevier Inc.201116519410.1016/B978‑0‑12‑384935‑9.10008‑2
     [Google Scholar]
  110. JinK.T. LuZ.B. ChenJ.Y. LiuY.Y. LanH.R. DongH.Y. YangF. ZhaoY.Y. ChenX.Y. Recent Trends in Nanocarrier-Based Targeted Chemotherapy: Selective Delivery of Anticancer Drugs for Effective Lung, Colon, Cervical, and Breast Cancer Treatment.J. Nanomater.20202020114[CrossRef].10.1155/2020/9184284
     [Google Scholar]
  111. TamV.H. SosaC. LiuR. YaoN. PriestleyR.D. Nanomedicine as a non-invasive strategy for drug delivery across the blood brain barrier.Int. J. Pharm.20165151-233134210.1016/j.ijpharm.2016.10.03127769885
     [Google Scholar]
  112. Masoudi AsilS. AhlawatJ. Guillama BarrosoG. NarayanM. Nanomaterial based drug delivery systems for the treatment of neurodegenerative diseases.Biomater. Sci.202081541094128[CrossRef].10.1039/D0BM00809E
     [Google Scholar]
  113. RahmanM.M. FerdousK.S. AhmedM. Emerging promise of nanoparticle-based treatment for Parkinson’s disease.Biointerface Res. Appl. Chem.2020201071357151
     [Google Scholar]
  114. De MarcoI. Supercritical Fluids and Nanoparticles in Cancer Therapy.Micromachines (Basel)2022139144910.3390/mi1309144936144072
     [Google Scholar]
  115. SaeediM. EslamifarM. KhezriK. DizajS.M. Applications of nanotechnology in drug delivery to the central nervous system.Biomed. Pharmacother.201911166667510.1016/j.biopha.2018.12.13330611991
     [Google Scholar]
  116. MoscarielloP. NgD.Y.W. JansenM. WeilT. LuhmannH.J. HedrichJ. Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates.Adv. Sci. (Weinh.)201855170089710.1002/advs.20170089729876217
     [Google Scholar]
  117. HolmesA.M. HeylingsJ.R. WanK.W. MossG.P. Antimicrobial efficacy and mechanism of action of poly(amidoamine) (PAMAM) dendrimers against opportunistic pathogens.Int. J. Antimicrob. Agents201953450050710.1016/j.ijantimicag.2018.12.01230599243
     [Google Scholar]
  118. EsumiK. HoudatsuH. YoshimuraT. Antioxidant action by gold- PAMAM dendrimer nanocomposites.Langmuir20042072536253810.1021/la036299r15835119
     [Google Scholar]
  119. OrtegaM.A. Guzmán MerinoA. Fraile-MartínezO. Recio-RuizJ. PekarekL. G GuijarroL. García-HonduvillaN. Álvarez-MonM. BujánJ. García-GallegoS. Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases.Pharmaceutics202012987410.3390/pharmaceutics1209087432937793
     [Google Scholar]
  120. ZhuY. LiuC. PangZ. Dendrimer-Based Drug Delivery Systems for Brain Targeting.Biomolecules201991279010.3390/biom912079031783573
     [Google Scholar]
  121. ChisA.A. DobreaC. MorgovanC. ArseniuA.M. RusL.L. ButucaA. JuncanA.M. TotanM. Vonica-TincuA.L. CormosG. MunteanA.C. MuresanM.L. GligorF.G. FrumA. Applications and Limitations of Dendrimers in Biomedicine.Molecules20202517398210.3390/molecules2517398232882920
     [Google Scholar]
  122. LeWittP.A. AradiS.D. HauserR.A. RascolO. The challenge of developing adenosine A2A antagonists for Parkinson disease: Istradefylline, preladenant, and tozadenant.Parkinsonism Relat. Disord.202080Suppl. 1S54S6310.1016/j.parkreldis.2020.10.02733349581
     [Google Scholar]
  123. PatonD.M. Paton, D.M. Istradefylline: adenosine A2A receptor antagonist to reduce “OFF” time in Parkinson’s disease.Drugs Today (Barc)202056212513410.1358/dot.2020.56.2.309815632163528
     [Google Scholar]
  124. Kadowaki HoritaT. KobayashiM. MoriA. JennerP. KandaT. Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex.Psychopharmacology (Berl.)2013230334535210.1007/s00213‑013‑3158‑x23748382
     [Google Scholar]
  125. BergerA.A. WinnickA. WelschmeyerA. KanebA. BerardinoK. CornettE.M. KayeA.D. ViswanathO. UritsI. Istradefylline to Treat Patients with Parkinson’s Disease Experiencing Istradefylline to Treat Patients with Parkinson’s Disease Experiencing “Off” Episodes: A Comprehensive Review.Neurol. Int.202012310912910.3390/neurolint1203001733302331
     [Google Scholar]
  126. AscherioA. ChenH. Caffeinated clues from epidemiology of Parkinson’s disease.Neurology20036111_suppl_6Suppl. 6S51S5410.1212/01.WNL.0000095213.86899.2114663011
     [Google Scholar]
  127. ChenJ.F. XuK. PetzerJ.P. StaalR. XuY.H. BeilsteinM. SonsallaP.K. CastagnoliK. CastagnoliN.Jr SchwarzschildM.A. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson’s disease.J. Neurosci.20012110RC14310.1523/JNEUROSCI.21‑10‑j0001.200111319241
     [Google Scholar]
  128. BibbianiF. OhJ.D. PetzerJ.P. CastagnoliN.Jr ChenJ.F. SchwarzschildM.A. ChaseT.N. A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease.Exp. Neurol.2003184128529410.1016/S0014‑4886(03)00250‑414637099
     [Google Scholar]
  129. XuK. BastiaE. SchwarzschildM. Therapeutic potential of adenosine A2A receptor antagonists in Parkinson’s disease.Pharmacol. Ther.2005105326731010.1016/j.pharmthera.2004.10.00715737407
     [Google Scholar]
  130. KandaT. JennerP. Can adenosine A2A receptor antagonists modify motor behavior and dyskinesia in experimental models of Parkinson’s disease?Parkinsonism Relat Disord.202080S1S21S2710.1016/j.parkreldis.2020.09.026
     [Google Scholar]
  131. FinkJ.S. WeaverD.R. RivkeesS.A. PeterfreundR.A. PollackA.E. AdlerE.M. ReppertS.M. Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum.Brain Res. Mol. Brain Res.199214318619510.1016/0169‑328X(92)90173‑91279342
     [Google Scholar]
  132. KondoT. MizunoY. Japanese Istradefylline Study Group A long-term study of istradefylline safety and efficacy in patients with Parkinson disease.Clin. Neuropharmacol.2015382414610.1097/WNF.000000000000007325768849
     [Google Scholar]
  133. SakoW. MurakamiN. MotohamaK. IzumiY. KajiR. The effect of istradefylline for Parkinson’s disease: A meta-analysis.Sci. Rep.2017711801810.1038/s41598‑017‑18339‑129269791
     [Google Scholar]
  134. TakahashiM. FujitaM. AsaiN. SakiM. MoriA. Safety and effectiveness of istradefylline in patients with Parkinson’s disease: interim analysis of a post-marketing surveillance study in Japan.Expert Opin. Pharmacother.201819151635164210.1080/14656566.2018.151843330281377
     [Google Scholar]
  135. GrondinR. BédardP.J. TaharA.H. GrégoireL. MoriA. KaseH. Antiparkinsonian effect of a new selective adenosine A 2A receptor antagonist in MPTP-treated monkeys.Neurology19995281673167710.1212/WNL.52.8.167310331698
     [Google Scholar]
  136. AoyamaS. KaseH. BorrelliE. Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an adenosine A2A receptor antagonist.J. Neurosci.200020155848585210.1523/JNEUROSCI.20‑15‑05848.200010908627
     [Google Scholar]
  137. WangM. LiL. ZhangX. LiuY. ZhuR. LiuL. FangY. GaoZ. GaoD. Magnetic resveratrol liposomes as a new theranostic platform for magnetic resonance imaging guided Parkinson’s disease targeting therapy.ACS Sustain. Chem.& Eng.2018612171241713310.1021/acssuschemeng.8b04507
     [Google Scholar]
  138. PinnaA. SerraM. MorelliM. SimolaN. Role of adenosine A2A receptors in motor control: relevance to Parkinson’s disease and dyskinesia.J. Neural Transm. (Vienna)201812581273128610.1007/s00702‑018‑1848‑629396609
     [Google Scholar]
  139. MoriA. ShindouT. Modulation of GABAergic transmission in the striatopallidal system by adenosine A2A receptors: a potential mechanism for the antiparkinsonian effects of A2A antagonists.Neurology.20036111S44S4810.1212/01.WNL.0000095211.71092.A0
     [Google Scholar]
  140. MoriA. How do adenosine A2A receptors regulate motor function?Parkinsonism Relat. Disord.202080Suppl. 1S13S2010.1016/j.parkreldis.2020.09.02533349575
     [Google Scholar]
  141. JennerP. Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson’s disease.Expert Opin. Investig. Drugs200514672973810.1517/13543784.14.6.72916004599
     [Google Scholar]
  142. Bara-JimenezW. SherzaiA. DimitrovaT. FavitA. BibbianiF. GillespieM. MorrisM.J. MouradianM.M. ChaseT.N. AdenosineA. Adenosine A 2A receptor antagonist treatment of Parkinson’s disease.Neurology200361329329610.1212/01.WNL.0000073136.00548.D412913186
     [Google Scholar]
  143. FuxeK. AgnatiL.F. JacobsenK. HillionJ. CanalsM. TorvinenM. Tinner-StainesB. StainesW. RosinD. TerasmaaA. PopoliP. LeoG. VergoniV. LluisC. CiruelaF. FrancoR. FerréS. Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson’s disease.Neurology20036111Suppl. 6S19S2314663004
     [Google Scholar]
  144. KachrooA. OrlandoL.R. GrandyD.K. ChenJ.F. YoungA.B. SchwarzschildM.A. Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice.J. Neurosci.20052545104141041910.1523/JNEUROSCI.3660‑05.200516280580
     [Google Scholar]
  145. CoccurelloR. BreysseN. AmalricM. Simultaneous blockade of adenosine A2A and metabotropic glutamate mGlu5 receptors increase their efficacy in reversing Parkinsonian deficits in rats.Neuropsychopharmacology20042981451146110.1038/sj.npp.130044415039773
     [Google Scholar]
  146. MoreJ.C.A. NisticoR. DolmanN.P. ClarkeV.R.J. AltA.J. OgdenA.M. BuelensF.P. TroopH.M. KellandE.E. PilatoF. BleakmanD. BortolottoZ.A. CollingridgeG.L. JaneD.E. Characterisation of UBP296: a novel, potent and selective kainate receptor antagonist.Neuropharmacology2004471466410.1016/j.neuropharm.2004.03.00515165833
     [Google Scholar]
  147. O’NeillM.J. MurrayT.K. WhalleyK. WardM.A. HicksC.A. WoodhouseS. OsborneD.J. SkolnickP. Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, in rodent models of Parkinson’s disease.Eur. J. Pharmacol.2004486216317410.1016/j.ejphar.2003.12.02314975705
     [Google Scholar]
  148. MarinoM.J. WilliamsD.L.Jr O’BrienJ.A. ValentiO. McDonaldT.P. ClementsM.K. WangR. DiLellaA.G. HessJ.F. KinneyG.G. ConnP.J. Allosteric modulation of group III metabotropic glutamate receptor 4: A potential approach to Parkinson’s disease treatment.Proc. Natl. Acad. Sci. USA200310023136681367310.1073/pnas.183572410014593202
     [Google Scholar]
  149. MishraA. GoelR.K. Modulatory Effect of Serotonergic System in Pentylenetetrazole-Induced Seizures and Associated Memory Deficit: Role of 5-HT<sub>1A</sub> and 5-HT<sub>2A/2C</sub>.J. Epilepsy Res.20199211912510.14581/jer.1901232509547
     [Google Scholar]
  150. MishraA. GoelR.K. Chronic 5-HT3 receptor antagonism ameliorates seizures and associated memory deficit in pentylenetetrazole-kindled mice.Neuroscience201633933931932810.1016/j.neuroscience.2016.10.01027746348
     [Google Scholar]
  151. BibbianiF. OhJ.D. ChaseT.N. Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models.Neurology200157101829183410.1212/WNL.57.10.182911723272
     [Google Scholar]
  152. SharifiH. Mohajjel NayebiaA. FarajniaS. The effect of chronic administration of buspirone on 6-hydroxydopamine-induced catalepsy in rats.Adv. Pharm. Bull.20122112713124312782
     [Google Scholar]
  153. BezardE. GerlachI. MoratallaR. GrossC.E. JorkR. 5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson’s disease.Neurobiol. Dis.2006231778610.1016/j.nbd.2006.02.00316545572
     [Google Scholar]
  154. GhiglieriV. MineoD. VannelliA. CacaceF. ManciniM. PendolinoV. NapolitanoF. di MaioA. MelloneM. StanicJ. TronciE. FidalgoC. StancampianoR. CartaM. CalabresiP. GardoniF. UsielloA. PicconiB. Modulation of serotonergic transmission by eltoprazine in L-DOPA-induced dyskinesia: Behavioral, molecular, and synaptic mechanisms.Neurobiol. Dis.20168614015310.1016/j.nbd.2015.11.02226639853
     [Google Scholar]
  155. CliveG. Ballard, David L. Kreitzman, Stuart Isaacson, I-Yuan Liu, James C. Norton, George Demos, Hubert H. Fernandez, Tihomir V. Ilic, Jean- Philippe Azulay, Joaquim J. Ferreira, Victor Abler, Srdjan Stankovic, 015 Study Group. Long-term evaluation of open-label pimavanserin safety and tolerability in Parkinson’s disease psychosis.Parkinsonism Relat. Disord.202077100106
     [Google Scholar]
  156. HamadjidaA. NuaraS.G. BédardD. GaudetteF. BeaudryF. GourdonJ.C. HuotP. The highly selective 5-HT2A antagonist EMD-281,014 reduces dyskinesia and psychosis in the l-DOPA-treated parkinsonian marmoset.Neuropharmacology2018139139616710.1016/j.neuropharm.2018.06.03829969592
     [Google Scholar]
  157. De DeurwaerdèreP. Di GiovanniG. MillanM.J. Expanding the repertoire of L-DOPA’s actions: A comprehensive review of its functional neurochemistry.Prog. Neurobiol.20171515710010.1016/j.pneurobio.2016.07.00227389773
     [Google Scholar]
  158. PolitisM. WuK. LoaneC. BrooksD.J. KiferleL. TurkheimerF.E. BainP. MolloyS. PicciniP. Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients.J. Clin. Invest.201412431340134910.1172/JCI7164024531549
     [Google Scholar]
  159. CartaM. CarlssonT. KirikD. BjörklundA. Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats.Brain200713071819183310.1093/brain/awm08217452372
     [Google Scholar]
  160. SvenningssonP. RosenbladC. af Edholm ArvidssonK. WictorinK. KeywoodC. ShankarB. LoweD.A. BjörklundA. WidnerH. Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study.Brain2015138496397310.1093/brain/awu40925669730
     [Google Scholar]
  161. Newman-TancrediA. AssiéM.B. LeducN. OrmièreA.M. DantyN. CosiC. Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia.Int. J. Neuropsychopharmacol.20058334135610.1017/S146114570400500015707540
     [Google Scholar]
  162. GrégoireL. SamadiP. GrahamJ. BédardP.J. BartoszykG.D. Di PaoloT. Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of l-Dopa in parkinsonian monkeys.Parkinsonism Relat. Disord.200915644545210.1016/j.parkreldis.2008.11.00119196540
     [Google Scholar]
  163. Hayashita-KinohH. YamadaM. YokotaT. MizunoY. MochizukiH. Down-regulation of α-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson’s disease rat model.Biochem. Biophys. Res. Commun.200634141088109510.1016/j.bbrc.2006.01.05716460685
     [Google Scholar]
  164. LewisJ. MelroseH. BumcrotD. HopeA. ZehrC. LincolnS. BraithwaiteA. HeZ. OgholikhanS. HinkleK. KentC. ToudjarskaI. CharisseK. BraichR. PandeyR.K. HeckmanM. MaraganoreD.M. CrookJ. FarrerM.J. in vivo silencing of alpha-synuclein using naked siRNA.Mol. Neurodegener.2008311910.1186/1750‑1326‑3‑1918976489
     [Google Scholar]
  165. GorbatyukO.S. LiS. NashK. GorbatyukM. LewinA.S. SullivanL.F. MandelR.J. ChenW. MeyersC. ManfredssonF.P. MuzyczkaN. in vivo RNAi-mediated alpha-synuclein silencing induces nigrostriatal degeneration.Mol. Ther.20101881450145710.1038/mt.2010.11520551914
     [Google Scholar]
  166. McCormackA.L. MakS.K. HendersonJ.M. BumcrotD. FarrerM.J. Di MonteD.A. Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.PLoS One201058e1212210.1371/journal.pone.001212220711464
     [Google Scholar]
  167. KhodrC.E. BecerraA. HanY. BohnM.C. Targeting alpha-synuclein with a microRNA-embedded silencing vector in the rat substantia nigra: Positive and negative effects.Brain Res.201415501550476010.1016/j.brainres.2014.01.01024463035
     [Google Scholar]
  168. CooperJ.M. WiklanderP.B.O. NordinJ.Z. Al-ShawiR. WoodM.J. VithlaniM. SchapiraA.H.V. SimonsJ.P. El-AndaloussiS. Alvarez-ErvitiL. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice.Mov. Disord.201429121476148510.1002/mds.2597825112864
     [Google Scholar]
  169. ZharikovA.D. CannonJ.R. TapiasV. BaiQ. HorowitzM.P. ShahV. El AyadiA. HastingsT.G. GreenamyreJ.T. BurtonE.A. shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson’s disease model.J. Clin. Invest.201512572721273510.1172/JCI6450226075822
     [Google Scholar]
  170. HelmschrodtC. HöbelS. SchönigerS. BauerA. BonicelliJ. GringmuthM. FietzS.A. AignerA. RichterA. RichterF. Polyethylenimine Nanoparticle-Mediated siRNA Delivery to Reduce α-Synuclein Expression in a Model of Parkinson’s Disease.Mol. Ther. Nucleic Acids201799576810.1016/j.omtn.2017.08.01329246324
     [Google Scholar]
  171. EversM.M. ToonenL.J.A. van Roon-MomW.M.C. Antisense oligonucleotides in therapy for neurodegenerative disorders.Adv. Drug Deliv. Rev.201587879010310.1016/j.addr.2015.03.00825797014
     [Google Scholar]
  172. WheelerT.M. LegerA.J. PandeyS.K. MacLeodA.R. NakamoriM. ChengS.H. WentworthB.M. BennettC.F. ThorntonC.A. Targeting nuclear RNA for in vivo correction of myotonic dystrophy.Nature2012488740911111510.1038/nature1136222859208
     [Google Scholar]
  173. YamamotoT. YaharaA. WakiR. YasuharaH. WadaF. Harada-ShibaM. ObikaS. Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo.Org. Biomol. Chem.201513123757376510.1039/C5OB00242G25690587
     [Google Scholar]
  174. ShankarJ. GeethaK.M. Barnabas Wilson, Potential applications of nanomedicine for treating Parkinson’s disease.J. Drug Deliv. Sci. Technol.20216610279310.1016/j.jddst.2021.102793
     [Google Scholar]
  175. NguyenT.T. Dung NguyenT.T. VoT.K. TranN.M.A. NguyenM.K. Van VoT. Van VoG. Nanotechnology-based drug delivery for central nervous system disorders.Biomed. Pharmacother.202114311211710.1016/j.biopha.2021.11211734479020
     [Google Scholar]
  176. IslamS.U. ShehzadA. AhmedM.B. LeeY.S. Intranasal delivery of nanoformulations: a potential way of treatment for neurological disorders.Molecules2020258192910.3390/molecules2508192932326318
     [Google Scholar]
  177. CouneP.G. SchneiderB.L. AebischerP. Parkinson’s disease: gene therapies.Cold Spring Harb. Perspect. Med.201224a00943110.1101/cshperspect.a00943122474617
     [Google Scholar]
  178. BorelF. KayM.A. MuellerC. Recombinant AAV as a platform for translating the therapeutic potential of RNA interference.Mol. Ther.201422469270110.1038/mt.2013.28524352214
     [Google Scholar]
  179. HaggertyD.L. GreccoG.G. ReevesK.C. AtwoodB. Adeno-Associated Viral Vectors in Neuroscience Research.Mol. Ther. Methods Clin. Dev.202017698210.1016/j.omtm.2019.11.01231890742
     [Google Scholar]
  180. HanH. YangJ. ChenW. LiQ. YangY. LiQ. A comprehensive review on histone-mediated transfection for gene therapy.Biotechnol. Adv.201937113214410.1016/j.biotechadv.2018.11.00930472306
     [Google Scholar]
  181. HudryE. VandenbergheL.H. Therapeutic AAV gene transfer to the nervous system: a clinical reality.Neuron2019101583986210.1016/j.neuron.2019.02.01730844402
     [Google Scholar]
  182. WuZ. AsokanA. SamulskiR.J. Adeno-associated virus serotypes: vector toolkit for human gene therapy.Mol. Ther.200614331632710.1016/j.ymthe.2006.05.00916824801
     [Google Scholar]
  183. WongL.F. GoodheadL. PratC. MitrophanousK.A. KingsmanS.M. MazarakisN.D. Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications.Hum. Gene Ther.20061711910.1089/hum.2006.17.116409120
     [Google Scholar]
  184. AxelsenT.M. WoldbyeD.P.D. Gene therapy for Parkinson’s disease, an update.J. Parkinsons Dis.20188219521510.3233/JPD‑18133129710735
     [Google Scholar]
  185. FiandacaM.S. BankiewiczK.S. Gene therapy for Parkinson’s disease: from non-human primates to humans.Curr. Opin. Mol. Ther.201012551952920886383
     [Google Scholar]
  186. CearleyC.N. WolfeJ.H. A single injection of an adeno-associated virus vector into nuclei with divergent connections results in widespread vector distribution in the brain and global correction of a neurogenetic disease.J. Neurosci.200727379928994010.1523/JNEUROSCI.2185‑07.200717855607
     [Google Scholar]
  187. FiandacaM.S. VarenikaV. EberlingJ. McKnightT. BringasJ. PivirottoP. BeyerJ. HadaczekP. BowersW. ParkJ. FederoffH. ForsayethJ. BankiewiczK.S. Real-time MR imaging of adeno-associated viral vector delivery to the primate brain.Neuroimage200947Suppl 2Suppl. 2T27T3510.1016/j.neuroimage.2008.11.01219095069
     [Google Scholar]
  188. HanlonK.S. MeltzerJ.C. BuzhdyganT. ChengM.J. Sena-EstevesM. BennettR.E. SullivanT.P. RazmpourR. GongY. NgC. NammourJ. MaizD. DujardinS. RamirezS.H. HudryE. MaguireC.A. Selection of an efficient AAV vector for robust CNS transgene expression.Mol. Ther. Methods Clin. Dev.20191532033210.1016/j.omtm.2019.10.00731788496
     [Google Scholar]
  189. RosarioA.M. CruzP.E. Ceballos-DiazC. StricklandM.R. SiemienskiZ. PardoM. SchobK.L. LiA. AslanidiG.V. SrivastavaA. GoldeT.E. ChakrabartyP. Microglia-specific targeting by novel capsid-modified AAV6 vectors.Mol. Ther. Methods Clin. Dev.201631602610.1038/mtm.2016.2627308302
     [Google Scholar]
  190. ChristineC.W. BankiewiczK.S. Van LaarA.D. RichardsonR.M. RavinaB. KellsA.P. BootB. MartinA.J. NuttJ. ThompsonM.E. LarsonP.S. Magnetic resonance imaging–guided phase 1 trial of putaminal AADC gene therapy for Parkinson’s disease.Ann. Neurol.201985570471410.1002/ana.2545030802998
     [Google Scholar]
  191. BernsK.I. MuzyczkaN. AAV: an overview of unanswered questions.Hum. Gene Ther.201728430831310.1089/hum.2017.04828335618
     [Google Scholar]
  192. GaoG. VandenbergheL. WilsonJ. New recombinant serotypes of AAV vectors.Curr. Gene Ther.20055328529710.2174/156652305406505715975006
     [Google Scholar]
  193. KantorB. BaileyR.M. WimberlyK. KalburgiS.N. GrayS.J. Methods for gene transfer to the central nervous system.Adv. Genet.20148712519710.1016/B978‑0‑12‑800149‑3.00003‑225311922
     [Google Scholar]
  194. McCartyD.M. Self-complementary AAV vectors; advances and applications.Mol. Ther.200816101648165610.1038/mt.2008.17118682697
     [Google Scholar]
  195. DuqueS. JoussemetB. RiviereC. MaraisT. DubreilL. DouarA.M. FyfeJ. MoullierP. ColleM.A. BarkatsM. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons.Mol. Ther.20091771187119610.1038/mt.2009.7119367261
     [Google Scholar]
  196. DominguezE. MaraisT. ChatauretN. Benkhelifa-ZiyyatS. DuqueS. RavassardP. CarcenacR. AstordS. de MouraA.P. VoitT. BarkatsM. Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice.Hum. Mol. Genet.201120468169310.1093/hmg/ddq51421118896
     [Google Scholar]
  197. FoustK.D. WangX. McGovernV.L. BraunL. BevanA.K. HaidetA.M. LeT.T. MoralesP.R. RichM.M. BurghesA.H.M. KasparB.K. RETRACTED ARTICLE: Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN.Nat. Biotechnol.201028327127410.1038/nbt.161020190738
     [Google Scholar]
  198. ValoriC.F. NingK. WylesM. MeadR.J. GriersonA.J. ShawP.J. AzzouzM. Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy.Sci. Transl. Med.201023535ra4210.1126/scitranslmed.300083020538619
     [Google Scholar]
  199. CroninJ. ZhangX.Y. ReiserJ. Altering the tropism of lentiviral vectors through pseudotyping.Curr. Gene Ther.20055438739810.2174/156652305454622416101513
     [Google Scholar]
  200. DullT. ZuffereyR. KellyM. MandelR.J. NguyenM. TronoD. NaldiniL. A third-generation lentivirus vector with a conditional packaging system.J. Virol.199872118463847110.1128/JVI.72.11.8463‑8471.19989765382
     [Google Scholar]
  201. NaldiniL. BlömerU. GallayP. OryD. MulliganR. GageF.H. VermaI.M. TronoD. in vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector.Science1996272525926326710.1126/science.272.5259.2638602510
     [Google Scholar]
  202. OlsenJ.C. Gene transfer vectors derived from equine infectious anemia virus.Gene Ther.19985111481148710.1038/sj.gt.33007689930301
     [Google Scholar]
  203. ZuffereyR. DullT. MandelR.J. BukovskyA. QuirozD. NaldiniL. TronoD. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery.J. Virol.199872129873988010.1128/JVI.72.12.9873‑9880.19989811723
     [Google Scholar]
  204. ZuffereyR. NagyD. MandelR.J. NaldiniL. TronoD. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo.Nat. Biotechnol.199715987187510.1038/nbt0997‑8719306402
     [Google Scholar]
  205. MerolaA. Van LaarA. LonserR. BankiewiczK. Gene therapy for Parkinson’s disease: contemporary practice and emerging concepts.Expert Rev. Neurother.202020657759010.1080/14737175.2020.176379432425079
     [Google Scholar]
  206. LindahlM. SaarmaM. LindholmP. Unconventional neurotrophic factors CDNF and MANF: structure, physiological functions and therapeutic potential.Neurobiol Dis.201797Pt B9010210.1016/j.nbd.2016.07.009
     [Google Scholar]
  207. JahanshahiM. ObesoI. BaunezC. AlegreM. KrackP. Parkinson’s D isease, the S ubthalamic N ucleus, I nhibition, and I mpulsivity.Mov. Disord.201530212814010.1002/mds.2604925297382
     [Google Scholar]
  208. ErlanderM.G. TillakaratneN.J.K. FeldblumS. PatelN. TobinA.J. Two genes encode distinct glutamate decarboxylases.Neuron1991719110010.1016/0896‑6273(91)90077‑D2069816
     [Google Scholar]
  209. LeeS.E. LeeY. LeeG.H. The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain.Arch. Pharm. Res.201942121031103910.1007/s12272‑019‑01196‑z31786745
     [Google Scholar]
  210. KaplittM.G. FeiginA. TangC. FitzsimonsH.L. MattisP. LawlorP.A. BlandR.J. YoungD. StrybingK. EidelbergD. DuringM.J. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial.Lancet200736995792097210510.1016/S0140‑6736(07)60982‑917586305
     [Google Scholar]
  211. LeWittP.A. RezaiA.R. LeeheyM.A. OjemannS.G. FlahertyA.W. EskandarE.N. KostykS.K. ThomasK. SarkarA. SiddiquiM.S. TatterS.B. SchwalbJ.M. PostonK.L. HendersonJ.M. KurlanR.M. RichardI.H. Van MeterL. SapanC.V. DuringM.J. KaplittM.G. FeiginA. AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham- surgery controlled, randomised trial.Lancet Neurol.201110430931910.1016/S1474‑4422(11)70039‑421419704
     [Google Scholar]
  212. NiethammerM. TangC.C. LeWittP.A. Long-term follow-up of a randomized AAV2-.JCI Insight201727e9013310.1172/jci.insight.9013328405611
     [Google Scholar]
  213. NiethammerM. TangC.C. VoA. NguyenN. SpetsierisP. DhawanV. MaY. SmallM. FeiginA. DuringM.J. KaplittM.G. EidelbergD. Gene therapy reduces Parkinson’s disease symptoms by reorganizing functional brain connectivity.Sci. Transl. Med.201810469eaau071310.1126/scitranslmed.aau071330487248
     [Google Scholar]
  214. SulzerD. EdwardsR.H. The physiological role of α-synuclein and its relationship to Parkinson’s Disease.J. Neurochem.2019150547548610.1111/jnc.1481031269263
     [Google Scholar]
  215. SpillantiniM.G. SchmidtM.L. LeeV.M.Y. TrojanowskiJ.Q. JakesR. GoedertM. α-Synuclein in Lewy bodies.Nature1997388664583984010.1038/421669278044
     [Google Scholar]
  216. JowaedA. SchmittI. KautO. WüllnerU. Methylation regulates alpha-synuclein expression and is decreased in Parkinson’s disease patients’ brains.J. Neurosci.201030186355635910.1523/JNEUROSCI.6119‑09.201020445061
     [Google Scholar]
  217. KantorB. TagliafierroL. GuJ. ZamoraM.E. IlichE. GrenierC. HuangZ.Y. MurphyS. Chiba-FalekO. Downregulation of SNCA expression by targeted editing of DNA methylation: a potential strategy for precision therapy in PD.Mol. Ther.201826112638264910.1016/j.ymthe.2018.08.01930266652
     [Google Scholar]
  218. WagnerJ. RyazanovS. LeonovA. LevinJ. ShiS. SchmidtF. PrixC. Pan-MontojoF. BertschU. Mitteregger-KretzschmarG. GeissenM. EidenM. LeidelF. HirschbergerT. DeegA.A. KrauthJ.J. ZinthW. TavanP. PilgerJ. ZweckstetterM. FrankT. BährM. WeishauptJ.H. UhrM. UrlaubH. TeichmannU. SamwerM. BötzelK. GroschupM. KretzschmarH. GriesingerC. GieseA. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease.Acta Neuropathol.2013125679581310.1007/s00401‑013‑1114‑923604588
     [Google Scholar]
  219. SinnigeT. YuA. MorimotoR.I. Challenging proteostasis: role of the chaperone network to control aggregation-prone proteins in human disease.Adv. Exp. Med. Biol.20201243536810.1007/978‑3‑030‑40204‑4_432297211
     [Google Scholar]
  220. SchwabK. FrahmS. HorsleyD. RickardJ.E. MelisV. GoatmanE.A. MagbagbeoluM. DouglasM. LeithM.G. BaddeleyT.C. StoreyJ.M.D. RiedelG. WischikC.M. HarringtonC.R. TheuringF. A protein aggregation inhibitor, leuco-methylthioninium bis(hydromethanesulfonate), decreases alpha-synu-clein inclusions in a transgenic mouse model of synucleinopathy.Front. Mol. Neurosci.20181044710.3389/fnmol.2017.0044729375308
     [Google Scholar]
  221. WrasidloW. TsigelnyI.F. PriceD.L. DuttaG. RockensteinE. SchwarzT.C. LedolterK. BonhausD. PaulinoA. EleuteriS. SkjevikÅ.A. KouznetsovaV.L. SpencerB. DesplatsP. Gonzalez-RuelasT. Trejo-MoralesM. OverkC.R. WinterS. ZhuC. ChesseletM.F. MeierD. MoesslerH. KonratR. MasliahE. A de novo compound targeting α-synuclein improves deficits in models of Parkinson’s disease.Brain2016139123217323610.1093/brain/aww23827679481
     [Google Scholar]
  222. Bengoa-VergnioryN. FaggianiE. Ramos-GonzalezP. KirkizE. Connor-RobsonN. BrownL.V. SiddiqueI. LiZ. VingillS. CiorochM. CavaliereF. ThrelfellS. RobertsB. SchraderT. KlärnerF.G. CraggS. DehayB. BitanG. MatuteC. BezardE. Wade-MartinsR. CLR01 protects dopaminergic neurons in vitro and in mouse models of Parkinson’s disease.Nat. Commun.2020111488510.1038/s41467‑020‑18689‑x32985503
     [Google Scholar]
  223. SimuniT. FiskeB. MerchantK. CoffeyC.S. KlingnerE. Caspell-GarciaC. Efficacy of Nilotinib in Patients With Moderately Advanced Parkinson Disease: A Randomized Clinical Trial.JAMA Neurol.20202020e204725
     [Google Scholar]
  224. PaganF.L. HebronM.L. WilmarthB. Torres-YaghiY. LawlerA. MundelE.E. YusufN. StarrN.J. AnjumM. ArellanoJ. HowardH.H. ShiW. MulkiS. Kurd-MistoT. MatarS. LiuX. AhnJ. MoussaC. Nilotinib effects on safety, tolerability, and potential biomarkers in parkinson disease: a phase 2 randomized clinical trial.JAMA Neurol.202077330931710.1001/jamaneurol.2019.420031841599
     [Google Scholar]
  225. EspayA.J. HauserR.A. ArmstrongM.J. The narrowing path for nilotinib and other potential disease-modifying therapies for parkinson disease.JAMA Neurol.202077329529710.1001/jamaneurol.2019.398331841588
     [Google Scholar]
  226. VolcD. PoeweW. KutzelniggA. LührsP. Thun-HohensteinC. SchneebergerA. GalabovaG. MajbourN. VaikathN. El-AgnafO. WinterD. MihailovskaE. MairhoferA. SchwenkeC. StafflerG. MedoriR. Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson’s disease: a randomised, single-blinded, phase 1 trial.Lancet Neurol.202019759160010.1016/S1474‑4422(20)30136‑832562684
     [Google Scholar]
  227. PardridgeW.M. Blood-brain barrier and delivery of protein and gene therapeutics to brain.Front. Aging Neurosci.20201137310.3389/fnagi.2019.0037331998120
     [Google Scholar]
  228. GastonJ. MaestraliN. LalleG. GagnaireM. MasieroA. DumasB. DabdoubiT. RadoševićK. BerneP.F. Intracellular delivery of therapeutic antibodies into specific cells using antibody-peptide fusions.Sci. Rep.2019911868810.1038/s41598‑019‑55091‑031822703
     [Google Scholar]
  229. JankovicJ. GoodmanI. SafirsteinB. MarmonT.K. SchenkD.B. KollerM. ZagoW. NessD.K. GriffithS.G. GrundmanM. SotoJ. OstrowitzkiS. BoessF.G. Martin-FacklamM. QuinnJ.F. IsaacsonS.H. OmidvarO. EllenbogenA. KinneyG.G. Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease.JAMA Neurol.201875101206121410.1001/jamaneurol.2018.148729913017
     [Google Scholar]
  230. CieślakM. KomoszyńskiM. WojtczakA. Adenosine A2A receptors in Parkinson’s disease treatment.Purinergic Signal.20084430531210.1007/s11302‑008‑9100‑818438720
     [Google Scholar]
  231. ZhengJ. ZhangX. ZhenX. Development of adenosine A.ACS Chem. Neurosci.201910278379110.1021/acschemneuro.8b0031330199223
     [Google Scholar]
  232. CervettoC. VenturiniA. PassalacquaM. GuidolinD. GenedaniS. FuxeK. Borroto-EsquelaD.O. CortelliP. WoodsA. MauraG. MarcoliM. AgnatiL.F. A2A-D2 receptor–receptor interaction modulates gliotransmitter release from striatal astrocyte processes.J. Neurochem.2017140226827910.1111/jnc.1388527896809
     [Google Scholar]
  233. Borroto-EscuelaD.O. HinzS. NavarroG. FrancoR. MüllerC.E. FuxeK. Understanding the role of adenosine A2AR heteroreceptor complexes in neurodegeneration and neuroinflammation.Front. Neurosci.2018124310.3389/fnins.2018.0004329467608
     [Google Scholar]
  234. VuorimaaA. RissanenE. AirasL. PET imaging of adenosine 2A receptors in neuroinflammatory and neurodegenerative disease.Contrast Media Mol. Imaging2017201711510.1155/2017/697584129348737
     [Google Scholar]
  235. ShindouT. MoriA. KaseH. IchimuraM. Adenosine A 2A receptor enhances GABA A -mediated IPSCs in the rat globus pallidus.J. Physiol.2001532242343410.1111/j.1469‑7793.2001.0423f.x11306661
     [Google Scholar]
  236. ShindouT. NonakaH. RichardsonP.J. MoriA. KaseH. IchimuraM. Presynaptic adenosine A2A receptors enhance GABAergic synaptic transmission via a cyclic AMP dependent mechanism in the rat globus pallidus.Br. J. Pharmacol.2002136229630210.1038/sj.bjp.070470212010779
     [Google Scholar]
  237. ShindouT. RichardsonP.J. MoriA. KaseH. IchimuraM. Adenosine modulates the striatal GABAergic inputs to the globus pallidus via adenosine A2A receptors in rats.Neurosci. Lett.2003352316717010.1016/j.neulet.2003.08.05914625011
     [Google Scholar]
  238. BeggiatoS. TomasiniM.C. BorelliA.C. Borroto-EscuelaD.O. FuxeK. AntonelliT. TanganelliS. FerraroL. Functional role of striatal A2A, D2, and mG lu5 receptor interactions in regulating striatopallidal GABA neuronal transmission.J. Neurochem.2016138225426410.1111/jnc.1365227127992
     [Google Scholar]
  239. GlaserT. AndrejewR. Oliveira-GiacomelliÁ. RibeiroD.E. Bonfim MarquesL. YeQ. RenW.J. SemyanovA. IllesP. TangY. UlrichH. Purinergic receptors in basal ganglia diseases: shared molecular mechanisms between Huntington’s and Parkinson’s Disease.Neurosci. Bull.202036111299131410.1007/s12264‑020‑00582‑833026587
     [Google Scholar]
  240. RodriguesR.J. AlfaroT.M. RebolaN. OliveiraC.R. CunhaR.A. Co-localization and functional interaction between adenosine A 2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum.J. Neurochem.200592343344110.1111/j.1471‑4159.2004.02887.x15659214
     [Google Scholar]
  241. ChenJ.F. CunhaR.A. The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson’s disease.Purinergic Signal.202016216717410.1007/s11302‑020‑09694‑232236790
     [Google Scholar]
  242. MishinaM. IshiwataK. NaganawaM. KimuraY. KitamuraS. SuzukiM. HashimotoM. IshibashiK. OdaK. SakataM. HamamotoM. KobayashiS. KatayamaY. IshiiK. Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson’s disease patients.PLoS One201162e1733810.1371/journal.pone.001733821386999
     [Google Scholar]
  243. IshibashiK. MiuraY. WagatsumaK. ToyoharaJ. IshiwataK. IshiiK. Occupancy of adenosine A2A receptors by istradefylline in patients with Parkinson’s disease using 11C-preladenant PET.Neuropharmacology201814310611210.1016/j.neuropharm.2018.09.03630253174
     [Google Scholar]
  244. FactorS.A. WolskiK. TogasakiD.M. HuyckS. CantillonM. HoT.W. HauserR.A. PourcherE. Long-term safety and efficacy of preladenant in subjects with fluctuating Parkinson’s disease.Mov. Disord.201328681782010.1002/mds.2539523589371
     [Google Scholar]
  245. HauserR.A. CantillonM. PourcherE. MicheliF. MokV. OnofrjM. HuyckS. WolskiK. Preladenant in patients with Parkinson’s disease and motor fluctuations: a phase 2, double-blind, randomised trial.Lancet Neurol.201110322122910.1016/S1474‑4422(11)70012‑621315654
     [Google Scholar]
  246. StocchiF. RascolO. HauserR.A. HuyckS. TzontchevaA. CapeceR. HoT.W. SklarP. LinesC. MichelsonD. HewittD.J. Preladenant Early Parkinson Disease Study Group Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease.Neurology201788232198220610.1212/WNL.000000000000400328490648
     [Google Scholar]
  247. HauserR.A. StocchiF. RascolO. HuyckS.B. CapeceR. HoT.W. SklarP. LinesC. MichelsonD. HewittD. Preladenant as an adjunctive therapy with levodopa in Parkinson disease: two randomized clinical trials and lessons learned.JAMA Neurol.201572121491150010.1001/jamaneurol.2015.226826523919
     [Google Scholar]
  248. HauserR.A. OlanowC.W. KieburtzK.D. PourcherE. Docu-AxeleradA. LewM. KozyolkinO. NealeA. ResburgC. MeyaU. KenneyC. BandakS. Tozadenant (SYN115) in patients with Parkinson’s disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial.Lancet Neurol.201413876777610.1016/S1474‑4422(14)70148‑625008546
     [Google Scholar]
  249. BrooksD.J. PapapetropoulosS. VandenhendeF. TomicD. HeP. CoppellA. O’NeillG. An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers.Clin. Neuropharmacol.2010332556010.1097/WNF.0b013e3181d137d220375654
     [Google Scholar]
  250. AminN. ByrneE. JohnsonJ. Chenevix-TrenchG. WalterS. NolteI.M. VinkJ.M. RawalR. ManginoM. TeumerA. KeersJ.C. VerwoertG. BaumeisterS. BiffarR. PetersmannA. DahmenN. DoeringA. IsaacsA. BroerL. WrayN.R. MontgomeryG.W. LevyD. PsatyB.M. GudnasonV. ChakravartiA. SulemP. GudbjartssonD.F. KiemeneyL.A. ThorsteinsdottirU. StefanssonK. van RooijF.J.A. AulchenkoY.S. HottengaJ.J. RivadeneiraF.R. HofmanA. UitterlindenA.G. HammondC.J. ShinS-Y. IkramA. WittemanJ.C.M. JanssensA.C.J.W. SniederH. TiemeierH. WolfenbuttelB.H.R. OostraB.A. HeathA.C. WichmannE. SpectorT.D. GrabeH.J. BoomsmaD.I. MartinN.G. van DuijnC.M. kConFab Investigators Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.Mol. Psychiatry201217111116112910.1038/mp.2011.10121876539
     [Google Scholar]
  251. HamzaT.H. ChenH. Hill-BurnsE.M. RhodesS.L. MontimurroJ. KayD.M. TenesaA. KuselV.I. SheehanP. EaaswarkhanthM. YearoutD. SamiiA. RobertsJ.W. AgarwalP. BordelonY. ParkY. WangL. GaoJ. VanceJ.M. KendlerK.S. BacanuS.A. ScottW.K. RitzB. NuttJ. FactorS.A. ZabetianC.P. PayamiH. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson’s disease modifier gene via interaction with coffee.PLoS Genet.201178e100223710.1371/journal.pgen.100223721876681
     [Google Scholar]
  252. PopatR.A. Van Den EedenS.K. TannerC.M. KamelF. UmbachD.M. MarderK. MayeuxR. RitzB. RossG.W. PetrovitchH. TopolB. McGuireV. CostelloS. ManthripragadaA.D. SouthwickA. MyersR.M. NelsonL.M. Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease.Eur. J. Neurol.201118575676510.1111/j.1468‑1331.2011.03353.x21281405
     [Google Scholar]
  253. YangA. PalmerA.A. de WitH. Genetics of caffeine consumption and responses to caffeine.Psychopharmacology (Berl.)2010211324525710.1007/s00213‑010‑1900‑120532872
     [Google Scholar]
  254. HoyerS. Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis.J. Neural Transm. (Vienna)1998105441542210.1007/s0070200500679720971
     [Google Scholar]
  255. BaggioL.L. DruckerD.J. Biology of Incretins: GLP-1 and GIP.Gastroenterology200713262131215710.1053/j.gastro.2007.03.05417498508
     [Google Scholar]
  256. LovshinJ.A. DruckerD.J. Incretin-based therapies for type 2 diabetes mellitus.Nat. Rev. Endocrinol.20095526226910.1038/nrendo.2009.4819444259
     [Google Scholar]
  257. AlvarezE. MartínezM.D. RonceroI. ChowenJ.A. García-CuarteroB. GispertJ.D. SanzC. VázquezP. MaldonadoA. De CáceresJ. DescoM. PozoM.A. BlázquezE. The expression of GLP-1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem.J. Neurochem.200592479880610.1111/j.1471‑4159.2004.02914.x15686481
     [Google Scholar]
  258. BertilssonG. PatroneC. ZachrissonO. AnderssonA. DannaeusK. HeidrichJ. KortesmaaJ. MercerA. NielsenE. RönnholmH. WikströmL. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of parkinson’s disease.J. Neurosci. Res.200886232633810.1002/jnr.2148317803225
     [Google Scholar]
  259. LiY. PerryT. KindyM.S. HarveyB.K. TweedieD. HollowayH.W. PowersK. ShenH. EganJ.M. SambamurtiK. BrossiA. LahiriD.K. MattsonM.P. HofferB.J. WangY. GreigN.H. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism.Proc. Natl. Acad. Sci. USA200910641285129010.1073/pnas.080672010619164583
     [Google Scholar]
  260. BassilF. CanronM.H. VitalA. BezardE. LiY. GreigN.H. GulyaniS. KapogiannisD. FernagutP.O. MeissnerW.G. Insulin resistance and exendin-4 treatment for multiple system atrophy.Brain201714051420143610.1093/brain/awx04428334990
     [Google Scholar]
  261. KimS. MoonM. ParkS. Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson’s disease.J. Endocrinol.2009202343143910.1677/JOE‑09‑013219570816
     [Google Scholar]
  262. AthaudaD. MaclaganK. SkeneS.S. Bajwa-JosephM. LetchfordD. ChowdhuryK. HibbertS. BudnikN. ZampedriL. DicksonJ. LiY. Aviles-OlmosI. WarnerT.T. LimousinP. LeesA.J. GreigN.H. TebbsS. FoltynieT. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial.Lancet2017390101031664167510.1016/S0140‑6736(17)31585‑428781108
     [Google Scholar]
  263. MarkakiI. WintherK. CatrinaS.B. SvenningssonP. Repurposing GLP1 agonists for neurodegenerative diseases.Int. Rev. Neurobiol.20201559111210.1016/bs.irn.2020.02.00732854860
     [Google Scholar]
  264. De SilvaA. SalemV. LongC.J. MakwanaA. NewbouldR.D. RabinerE.A. GhateiM.A. BloomS.R. MatthewsP.M. BeaverJ.D. DhilloW.S. The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans.Cell Metab.201114570070610.1016/j.cmet.2011.09.01022000927
     [Google Scholar]
  265. SchlöglH. KabischS. HorstmannA. LohmannG. MüllerK. LepsienJ. Busse-VoigtF. KratzschJ. PlegerB. VillringerA. StumvollM. Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity.Diabetes Care20133671933194010.2337/dc12‑192523462665
     [Google Scholar]
  266. AthaudaD. GulyaniS. KarnatiH. LiY. TweedieD. MustapicM. ChawlaS. ChowdhuryK. SkeneS.S. GreigN.H. KapogiannisD. FoltynieT. Utility of neuronal-derived exosomes to examine molecular mechanisms that affect motor function in patients with Parkinson disease: a secondary analysis of the exenatide-PD trial.JAMA Neurol.201976442042910.1001/jamaneurol.2018.430430640362
     [Google Scholar]
  267. OakleyA.E. CollingwoodJ.F. DobsonJ. LoveG. PerrottH.R. EdwardsonJ.A. ElstnerM. MorrisC.M. Individual dopaminergic neurons show raised iron levels in Parkinson disease.Neurology200768211820182510.1212/01.wnl.0000262033.01945.9a17515544
     [Google Scholar]
  268. WardR.J. ZuccaF.A. DuynJ.H. CrichtonR.R. ZeccaL. The role of iron in brain ageing and neurodegenerative disorders.Lancet Neurol.201413101045106010.1016/S1474‑4422(14)70117‑625231526
     [Google Scholar]
  269. DexterD.T. StattonS.A. WhitmoreC. FreinbichlerW. WeinbergerP. TiptonK.F. Della CorteL. WardR.J. CrichtonR.R. Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson’s disease after peripheral administration.J. Neural Transm. (Vienna)2011118222323110.1007/s00702‑010‑0531‑321165659
     [Google Scholar]
  270. DevosD. MoreauC. DevedjianJ.C. KluzaJ. PetraultM. LalouxC. JonneauxA. RyckewaertG. GarçonG. RouaixN. DuhamelA. JissendiP. DujardinK. AugerF. RavasiL. HopesL. GrolezG. FirdausW. SablonnièreB. Strubi-VuillaumeI. ZahrN. DestéeA. CorvolJ.C. PöltlD. LeistM. RoseC. DefebvreL. MarchettiP. CabantchikZ.I. BordetR. Targeting chelatable iron as a therapeutic modality in Parkinson’s disease.Antioxid. Redox Signal.201421219521010.1089/ars.2013.559324251381
     [Google Scholar]
/content/journals/cdt/10.2174/0113894501312703240826070530
Loading
Trends on Novel Targets and Nanotechnology-Based Drug Delivery System in the Treatment of Parkinson's disease: Recent Advancement in Drug Development
Curr Drug Targets 25, 987 (2024); https://doi.org/10.2174/0113894501312703240826070530
/content/journals/cdt/10.2174/0113894501312703240826070530
/content/journals/cdt/10.2174/0113894501312703240826070530
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): BBB; dopamine; levodopa; motor activity; Parkinsonism; α-synuclein

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test