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CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Current Issue
Volume 24, Issue 3, 2025
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Noninvasive Therapies: A Forthcoming Approach to Parkinson's Treatment
Authors: Umer Anayyat, Faiza Ahad, Bushra Muhammad Fordil, Hajra Hameed, Mengqing Li, Qinyao Yu, Yunpeng Wei and Xiaomei WangIn this review, we have discussed the invasive and non-invasive treatment options for Parkinson’s Disease (PD) following their safety, specificity, and reliability. Initially, this study has highlighted the invasive treatment options and the side effects they possess. A deep understanding of L-Dopa treatment, as oral or infusion, and the use of dopamine agonists has indicated that there is a need to acquire an alternative treatment for PD. The combined therapy with L-Dopa has been proven to affect PD, but with some limitations, such as mild to chronic side effects, with particular requirements of age and health of the patient and a large amount of expenditure. In the discussion of noninvasive methods to treat PD, we have found that this approach is comparatively slow and requires repetitive sessions, but is safe, effective, and reliable at any stage of PD. Electroconvulsive therapy has revealed its effectiveness in various neurological diseases, including PD. Transcranial current stimulation (direct or alternative) has already been shown to have an alleviative response to PD symptoms. Transcranial magnetic stimulations and other strategies of using the magnetic field for potential treatment options for PD need to be explored further imminently.
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A Comprehensive Review on Repurposing the Nanocarriers for the Treatment of Parkinson’s Disease: An Updated Patent and Clinical Trials
Authors: Sara Khan and Md. Faheem HaiderParkinson's Disease (PD) is a progressive neurodegenerative disorder marked by the deterioration of dopamine-producing neurons, resulting in motor impairments like tremors and rigidity. While the precise cause remains elusive, genetic and environmental factors are implicated. Mitochondrial dysfunction, oxidative stress, and protein misfolding contribute to the disease's pathology. Current therapeutics primarily aim at symptom alleviation, employing dopamine replacement and deep brain stimulation. However, the quest for disease-modifying treatments persists. Ongoing clinical trials explore novel approaches, such as neuroprotective agents and gene therapies, reflecting the evolving PD research landscape. This review provides a comprehensive overview of PD, covering its basics, causal factors, major pathways, existing treatments, and a nuanced exploration of ongoing clinical trials. As the scientific community strives to unravel PD's complexities, this review offers insights into the multifaceted strategies pursued for a better understanding and enhanced management of this debilitating condition.
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Exploring Therapeutic Strategies: The Relationship between Metabolic Disorders and FOXO Signalling in Alzheimer's Disease
Alzheimer’s disease is an ailment that is linked with the degeneration of the brain cells, and this illness is the main cause of dementia. Metabolic stress affects the activity of the brain in AD via FOXO signaling. The occurrence of AD will significantly surge as the world’s population ages, along with lifestyle changes perceived in current decades, indicating a main contributor to such augmented prevalence. Similarly, metabolic disorders of current adulthood, such as obesity, stroke, and diabetes mellitus, have been observed as the risk-causing factors of AD. Environmental influences induce genetic mutations that result in the development of several diseases. Metabolic disorders develop when individuals are exposed to an environment where food is easily accessible and requires minimal energy expenditure. Obesity and diabetes are among the most significant worldwide health concerns. Obesity arises because of an imbalance between the amount of energy consumed and the amount of energy expended, which is caused by both behavioral and physiological factors. Obesity, insulin resistance syndrome, hypertension, and inflammation are factors that contribute to the worldwide risk of developing diabetes mellitus and neurodegenerative diseases. FOXO transcription factors are preserved molecules that play an important part in assorted biological progressions, precisely in aging as well as metabolism. Apoptosis, cell division and differentiation, oxidative stress, metabolism, and lifespan are among the physiological processes that the FOXO proteins are adept at controlling. In this review, we explored the correlation between signaling pathways and the cellular functions of FOXO proteins. We have also summarized the intricate role of FOXO in AD, with a focus on metabolic stress, and discussed the prospect of FOXO as a molecular link between AD and metabolic disorders.
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Hypoxia-inducible Factor-1α Pathway in Cerebral Ischemia: From Molecular Mechanisms to Therapeutic Targets
Authors: Veerta Sharma and Thakur Gurjeet SinghIntroductionIschemic injury to the brain can result in a variety of life-threatening conditions, mortality, or varying degrees of disability. Hypoxia-inducible factor 1α (HIF 1α), an oxygen-sensitive transcription factor that controls the adaptive metabolic response to hypoxia, is a critical constituent of cerebral ischemia. It participates in numerous processes, such as metabolism, proliferation, and angiogenesis, and plays a major role in cerebral ischemia.
MethodsThrough the use of a number of different search engines like Scopus, PubMed, Bentham, and Elsevier databases, a literature review was carried out for investigating the pharmacological modulation of HIF-1α pathways for the treatment of cerebral ischemia.
ResultsVarious signalling pathways, such as Mitogen-activated protein kinase (MAPK), Janus kinase/signal transducers and activators (JAK/STAT), Phosphoinositide-3-kinase (PI3-K), and cAMP-response element binding protein (CREB) play a vital role in modulation of HIF-1α pathway, which helps in preventing the pathogenesis of cerebral ischemia.
ConclusionThe pharmacological modulation of the HIF-1α pathway via various molecular signalling pathways, such as PI3-K, MAPK, CREB, and JAK/STAT activators, offer a promising prospect for future interventions and treatment for cerebral ischemia.
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Recent Development of Zolmitriptan Formulation in Migraine Therapy: Production, Metabolism and Pharmaceutical Aspects
The triptans class of pharmaceuticals, which was created to treat acute migraine, is made up of indole-containing drugs that bind to a subset (1B/1D) of 5-hydroxytryptamine receptors and are agonists of serotonin receptors. At the moment, naratriptan, eletriptan, zolmitriptan, rizatriptan, almotriptan, and frovatriptan are the seven types of triptans available on the market. Among these are the FDA-approved triptans, Zolmitriptan and Sumatriptan, which are selective serotonin (5-hydroxytryptamine) agonists. Zolmitriptan, a synthetic tryptamine derivative and a well-known member of the triptan family, is available as an orally disintegrating tablet, nasal spray, and tablet. There are melt formulations of rizatriptan and zolmitriptan available on the market that are easier to use and absorb, comparable to regular pills. Recently, the FDA approved zolmitriptan, a medication with tolerability comparable to sumatriptan. Whereas zolmitriptan is only available as an oral melt or tablet, sumatriptan is available as a nasal spray, oral preparation, or self-injectable kit. The only known antimigraine drugs that were widely utilized before the triptan period were ergotamine and dihydroergotamine. However, zolmitriptan binds to plasma proteins only 25% of the time because of significant first-pass degradation. Researchers have looked into fresh ideas for solving this issue and innovations to overcome its pharmacokinetic difficulties. This article emphasizes the role of zolmitriptan in the treatment of migraines, highlighting its pharmacological properties, production, metabolism, and structural features.
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The Alpha-7 Nicotinic Receptor Positive Allosteric Modulator PNU120596 Attenuates Lipopolysaccharide-Induced Depressive-Like Behaviors and Cognitive Impairment by Regulating the PPAR-α Signaling Pathway in Mice
Authors: Sami Alzarea and Shafiqur RahmanBackground and ObjectiveThe brain α7 nicotinic acetylcholine receptor (α7 nAChR) has a critical role in the pathophysiology of Major Depressive Disorder (MDD) involving neuroinflammation. The α7 nAChR stimulation has been shown to modulate the anti-inflammatory effects of nuclear peroxisome proliferator-activated receptor-α (PPAR-α) via its endogenous ligands in the brain. The present study determined the effects of α7 nAChR modulator PNU120596 on PPAR-α, an inhibitor of κB (IκB) and nuclear factor-κB (NF-κB) expression and interleukin-1β (IL-1β) level in the hippocampus and prefrontal cortex (PFC) in an inflammatory mouse model of MDD induced by lipopolysaccharide (LPS). We also evaluated the combined effects of PNU120596 and GW6471, a PPAR-α antagonist, on depressive-like and cognitive deficit-like behaviors in mice.
Materials and MethodsMale C57BL/6J mice were treated with PNU120596, followed by systemic LPS (1 mg/kg, i.p.) administration. The effects of PNU120596 on the mRNA expression of PPAR-α and IκB were assessed in the hippocampus and PFC using qRT-PCR following LPS administration. Similarly, the effects of PNU120596 on the immunoreactivity of PPAR-α and NF-κB were measured in the hippocampus and PFC using an immunofluorescence assay. Furthermore, the effects of PNU120596 on pro-inflammatory cytokine IL-1β levels were measured in the hippocampus and PFC using ELISA. The combined effects of PNU120596 and GW6471 were also assessed against LPS-induced depressive-like and cognitive deficit-like behaviors using the Tail Suspension Test (TST), Forced Swim Test (FST), and Y-maze test.
ResultsPNU120596 (4 mg/kg) significantly prevented LPS-induced dysregulation of PPAR-α, IκB, p-NF-κB p65, and IL-1β in the hippocampus and PFC. Pretreatment with PNU120596 showed significant antidepressant-like effects by reducing immobility time in the TST and FST. Similarly, pretreatment with PNU120596 significantly reduced cognitive deficit-like behavior in the Y-maze test. The antidepressant and pro-cognitive-like effects of PNU120596 were reversed by PPAR-α antagonist GW6471 (2 mg/kg).
ConclusionThese results suggest that PNU120596 prevented LPS-induced MDD and cognitive-like behavior by regulating α7 nAChR/PPAR-α signaling pathway in the hippocampus and PFC.
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Volumes & issues
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Volume 24 (2025)
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Volume 23 (2024)
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Volume 22 (2023)
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Volume 21 (2022)
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Volume 20 (2021)
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Volume 19 (2020)
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Volume 18 (2019)
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Volume 17 (2018)
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Volume 16 (2017)
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Volume 15 (2016)
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Volume 14 (2015)
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Volume 13 (2014)
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Volume 12 (2013)
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Volume 11 (2012)
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Volume 10 (2011)
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Volume 9 (2010)
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Volume 8 (2009)
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Volume 7 (2008)
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Volume 6 (2007)
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Volume 5 (2006)
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A Retrospective, Multi-Center Cohort Study Evaluating the Severity- Related Effects of Cerebrolysin Treatment on Clinical Outcomes in Traumatic Brain Injury
Authors: Dafin F. Muresanu, Alexandru V. Ciurea, Radu M. Gorgan, Eva Gheorghita, Stefan I. Florian, Horatiu Stan, Alin Blaga, Nicolai Ianovici, Stefan M. Iencean, Dana Turliuc, Horia B. Davidescu, Cornel Mihalache, Felix M. Brehar, Anca . S. Mihaescu, Dinu C. Mardare, Aurelian Anghelescu, Carmen Chiparus, Magdalena Lapadat, Viorel Pruna, Dumitru Mohan, Constantin Costea, Daniel Costea, Claudiu Palade, Narcisa Bucur, Jesus Figueroa and Anton Alvarez
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