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- Volume 17, Issue 12, 2017
Current Topics in Medicinal Chemistry - Volume 17, Issue 12, 2017
Volume 17, Issue 12, 2017
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HTLV-1 Associated Neurological Disorders
Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic to certain regions of the world and infects around 10-20 million people. HTLV-1 is the etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated neurological disorders including mainly HTLV-1 associated myelopathy/Tropical spastic paraparesis. The involvement of the central nervous diseases occurs among: HTLV-1 infected patients from endemic areas, HIV positive individuals and drug users. The ability of HTLV-1 to cause associated neuropathies starts with the virus crossing the blood brain barrier (BBB), then entering and infecting the cells of the central nervous system. As a consequence, to the viral attack, HTLV-1 infected lymphocytes produce pro-inflammatory cytokines like tumor necrosis factor alpha, Interleukin 1 beta and interleukin 6 which further disrupts the BBB. Different serological tests have been used in the diagnosis of HTLV-1. These include: ELISA, Western Blotting (WB), Immunofluorescence, Particle Agglutination and Polymerase Chain Reaction which is used as a confirmatory test. Danazol, pentoxifylline, azathioprine and vitamin C have been used in the treatment of the HTLV-1 associated neurological disorders. Other antiviral drugs (lamivudine, zidovudine), monoclonal antibodies (Daclizumab) and therapeutic agents (valporic acid, interferons) have also been evaluated. No known drug, so far, has been shown to be efficacious. The aim of this review is to present the complexities of HTLV-1 associated neurological disorders and their current ongoing treatment. In addition to discussing future possible therapeutic strategies, by targeting HTVL-1 viral components and gene/s products, for the treatment of those neurological conditions.
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Type 3 Diabetes Mellitus: A Novel Implication of Alzheimers Disease
Authors: Jerzy Leszek, Elzbieta Trypka, Vadim V. Tarasov, Ghulam Md Ashraf and Gjumrakch AlievThe brain of patients with Alzheimer disease (AD) showed the evidence of reduced expression of insulin and neuronal insulin receptors, as compared with those of age-matched controls. This event gradually and certainly leads to a breakdown of the entire insulin-signaling pathway, which manifests insulin resistance. This in turn affects brain metabolism and cognitive functions, which are the bestdocumented abnormalities in AD. These observations led Dr. de la Monte and her colleagues to suggest that AD is actually a neuroendocrine disorder that resembles type 2 diabetes mellitus. The truth would be more complex with understanding the role of low-density lipoprotein receptor-related protein 1, Aβ derived diffusible ligands, and advanced glycation end products. However, now it known as “brain diabetes” and is called type 3 diabetes mellitus (T3DM). This review provides an overview of “brain diabetes” focusing on the reason why the phenomenon is called T3DM.
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Oxidative Stress and Antioxidant Potential of One Hundred Medicinal Plants
Reactive species are produced in biological system because of redox reactions. The imbalance in pro-oxidant and antioxidant homeostasis leads to the production of toxic reactive oxygen and nitrogen species like hydrogen peroxide, organic peroxides, hydroxyl radicals, superoxide anion and nitric oxide. Inactivation of metabolic enzymes, oxidation of biomolecules and cellular damage are some of the prominent characteristics of reactive species. Similarly, oxidative stress has been associated with more than one hundred (100) pathologies such as atherosclerosis, diabetes, cardiovascular diseases, pancreatic and liver diseases, joint disorders, cardiac fibrosis, acute respiratory distress syndrome, neurological diseases (amyotrophic lateral sclerosis, Huntington’s disorder, Parkinson’s disease and Alzheimer’s disease), ageing and cancer etc. The toxicity of reactive species is balanced by the integrated antioxidant systems, which include enzymatic and non-enzymatic antioxidants. Antioxidant therapies or defenses protect the biological sites by removing or quenching the free radicals (prooxidants). Medicinal plants can not only protect the oxidative damage, but also play a vital role in health maintenance and prevention of chronic degenerative diseases. This review will provide a valuable discussion of one hundred (100) well known medicinal plants, which may add to the optimization of antioxidants rank. Besides, some of the antioxidant evaluation techniques or mechanisms via which medicinal plants act as antioxidants are also described.
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Synopsis on Managment Strategies for Neurodegenerative Disorders: Challenges from Bench to Bedside in Successful Drug Discovery and Development
More LessThe maintenance of health requires successful cell functioning, which in turn depends upon the proper and active conformation of proteins besides other biomolecules. However, occasionally these proteins may misfold and lead to the appearance and progression of protein conformational diseases. These diseases apart from others include several neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson disease, Huntington’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and other lesser known diseases. Although much knowledge has been gained, these NDDs still warrant advance research in the elucidation of their mechanisms as well as effective therapeutic interventions and proper management. There is an ever-growing and urgent need to improve the diagnosis and management of NDDs due to their devastating nature, serious social impact and neuropsychiatric symptoms. It is also envisioned that we may be able to encourage, develop, and strengthen the cell defenses against amyloid toxicity and prevent neuronal destruction and consequently neurodegeneration. In this review, the implications of protein misfolding and aggregation in NDDs are discussed along with some of the most recent findings on the curative and beneficial effects of natural molecules such as polyphenols. This paper also reviews the anti-aggregation and protective effects of some organic and peptidic compounds duly supported experimentally, as prospective future therapeutics for NDDs. The synopses presented in this review shall prove helpful in further understanding of the causes, cures and management of lethal NDDs.
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Nanotechnology in Neuroscience and its Perspective as Gene Carrier
Authors: T. M.T. Khanh, D. Wei, P. H.L. Tran and Thao T.D. TranGene therapy has a strong potential in neuroscience by suppressing or replacing abnormalities in genetic materials. The employment of nano-gene carrier for neurological disorders is comparatively young and restricted since the aim to effectively deliver therapeutic agents into the central nervous system (CNS) commonly has confronted difficulties of several natural occurring barriers in the body and unfavorable characteristics of pharmaceutical agents. Two major anatomical and biochemical barriers are blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), which significantly prevent permeation of most drugs and genes to brain parenchyma. In this concern, nanotechnology emerges as an innovative method for transporting therapeutics to the CNS. Diverse nano-systems have been closely investigated, some of which have demonstrated initial success for in vivo studies. The perspectives of nanotechnology for gene therapy would be a promising field to be further explored in the near future.
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Infectious Agents and Neurodegenerative Diseases: Exploring the Links
Recent studies have shown that bacterial and viral infections are risk factors for various neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Multiple Sclerosis (MS), Alzheimer’s disease (AD), and Lyme disease (LD). However, it is still controversial how the infections play a role in neurological diseases progression. Infections in central nervous system may lead multiple damages in infected and neighboring cells. The infection leads to the activation of inflammatory processes and host immune responses, which acts as defense mechanism and also causes damage to the host neuronal functions and viability. Several bacterial and viral pathogens have been reported for neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in combination with other factors, like aging, metabolic diseases and the genetic makeup of the host. We will focus in this review on the possible link between neurodegeneration and infections particularly Chlamydophila pneumoniae, Borrelia burgdorferi, Mycoplasma etc.
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Elucidating Treatment of Alzheimer's Disease via Different Receptors
Alzheimer’s disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. Presently, it is the most common reason for the memory loss and dementia in older individuals. It is patho-physiologically described by extracellular amyloid beta (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) retention, neuronal decline, and neurotransmitter system derangement. Various receptors such as nicotinic acetylcholine, N-methyl-D-aspartate, insulin, serotonin, adenosine, and histamine are actively involved in the physiological progression of AD. Till date memantine and only four other acetylcholinesterase inhibitors have been approved for the treatment of AD by US Food and Drug Administration (US-FDA). Hence, there is a critical need to explore and develop novel and helpful management systems which could specifically target different receptors involved in AD progression. We believe that these receptors targeting will either impede the disease onset or slow down its pathogenesis. In the present review, we tried to uncover some receptors that could be blocked by novel inhibitors and ultimately used for the therapeutic management of AD.
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Alzheimer's Disease and Natural Products: Future Regimens Emerging from Nature
Alzheimer’s disease (AD), which largely affects the elderly, has become a global burden. Patients with AD have both short- and long-term memory impairments. The neuronal loss in AD occurs due to abnormally folded amyloid beta proteins and aggregation of hyperphosphorylated tau proteins in the brain. Eventually, amyloid plaques and neurofibrillary tangles are formed, which subsequently disintegrate the neuronal transport system. There are several factors which are involved in AD pathogenesis, including oxidative stress, inflammation and the presence of metal ions. The modern therapies utilized for AD treatment have many adverse effects, driving the quest for more safe and effective medications. Many dietary components, including different types of fruits, vegetables, spices, and marine products as well as a Mediterranean diet, are a good source of antioxidants and have anti-inflammatory properties, with many showing substantial potential against AD pathogenesis. In this review, we discuss the potential of these foods for treating AD and opportunities for developing disease-targeted drugs from active compounds extracted from natural dietary products.
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Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players
Glucose homeostasis is crucial for neuronal survival, synaptic plasticity, and is indispensable for learning and memory. Reduced sensitivity of cells to insulin and impaired insulin signaling in brain neurons participate in the pathogenesis of Alzheimer disease (AD). The tumor suppressor protein p53 coordinates with multiple cellular pathways in response to DNA damage and cellular stresses. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic metabolites (e.g. ceramide and products of advanced glycation) and ROS-modified cellular components, together with the activation of proapoptotic genes, could finally induce a suicide death program of autophagy/apoptosis in neurons. Recent studies reveal the impact of p53 on expression and processing of several microRNAs (miRs) under DNA damage-inducing conditions. Additionally, the role of miRs in promotion of insulin resistance and type 2 diabetes mellitus has been well documented. Detailed recognition of the role of p53/miRs crosstalk in driving insulin resistance in AD brains could improve the disease diagnostics and aid future therapy.
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Gliomas: New Perspectives in Diagnosis, Treatment and Prognosis
Gliomas are central nervous system tumors originated from glial cells, whose incidence and mortality is expected to rise in coming years, especially in developing countries. Diagnosis and classification of gliomas have largely relied on tumor histopathologic features that provide limited information regarding response to therapy or prognosis. Current treatment of gliomas is surgery combined with chemotherapy and/or radiotherapy. However, many tumors show a high resistance to these interventions, and recurrences are frequent since conventional therapies do not take into account the unique molecular features of different subtypes of glioma. Molecular genetics provide new insights in classifying gliomas and predicting response to therapy that can range from conventional treatments to new revolutionary therapeutic approaches. This article offers a review of the intracellular signaling pathways involved in carcinogenesis of gliomas, as well as a description of new tools for their diagnosis, prognosis, and treatment with a target-oriented approach.
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Volumes & issues
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Volume 24 (2024)
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Volume 23 (2023)
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Volume 22 (2022)
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Volume 21 (2021)
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Volume 20 (2020)
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Volume 19 (2019)
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Volume 18 (2018)
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Volume 17 (2017)
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Volume 16 (2016)
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Volume 15 (2015)
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Volume 14 (2014)
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Volume 13 (2013)
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Volume 12 (2012)
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Volume 11 (2011)
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Volume 10 (2010)
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Volume 9 (2009)
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Volume 8 (2008)
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Volume 7 (2007)
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Volume 6 (2006)
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Volume 5 (2005)
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Volume 4 (2004)
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Volume 3 (2003)
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Volume 2 (2002)
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Volume 1 (2001)