CNS & neurological disorders drug targets最新文献

{"title":"An Updated Review of Epigenetic-Related Mechanisms and their Contribution to Multiple Sclerosis Disease.","authors":"Maedeh Eslahi,&nbsp;Negin Nematbakhsh,&nbsp;Narges Dastmalchi,&nbsp;Shahram Teimourian,&nbsp;Reza Safaralizadeh","doi":"10.2174/1871527321666220119104649","DOIUrl":"https://doi.org/10.2174/1871527321666220119104649","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is a multifactorial, neurodegenerative, and inflammatory demyelination disease with incomplete remyelination in the CNS. It would be more informative to reveal the underlying molecular mechanisms of MS. Molecular mechanisms involving epigenetic changes play a pivotal role in this disease. Epigenetic changes impact gene expression without altering the underlying DNA sequence. The main epigenetic modifications that play a key role in the regulation of gene expression principally include DNA methylation, histone modifications, and microRNA- associated post-transcriptional gene silencing. In this review, we summarize the dynamics of epigenetic changes and their relation to environmental risk factors in MS pathogenesis. Studies suggest that epigenetic changes have a role in the development of MS and environmental risk factors, such as vitamin D, smoking, and Epstein-Barr virus infection seem to influence the development and susceptibility to MS. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the diseases, which shows complicated pathogenesis. Epigenetic research has the potential to complete our understanding of MS initiation and progression. Increased understanding of MS molecular pathways leads to new insights into potential MS therapies. However, there is a need for in vivo evaluation of the role of epigenetic factors in MS therapy. It would be more valuable to indicate the role of various epigenetic factors in MS.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 3","pages":"381-393"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9149923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine as a Potential Target for Learning and Memory: Contributing to Related Neurological Disorders.","authors":"Masoumeh Kourosh-Arami,&nbsp;Alireza Komaki,&nbsp;Mohammad-Reza Zarrindast","doi":"10.2174/1871527321666220418115503","DOIUrl":"https://doi.org/10.2174/1871527321666220418115503","url":null,"abstract":"<p><p>It is well established that learning and memory are complex processes. They involve and recruit different brain modulatory neurotransmitter systems. Considerable evidence points to the involvement of dopamine (DA) in learning and memory. Manifestations of the synaptic spatial localization of the effect of DA have gained a great deal of interest. Despite the molecular cloning of the five DA receptor subtypes, the underlying signaling of the DA receptors in spatial learning and memory is less compelling. Fluctuations in the DA level in the brain are associated with many diseases that comprise deficits in learning and memory, including Parkinson's disease, Huntington's disease, schizophrenia, and Alzheimer's disease. This review aims to briefly summarize existing information regarding the memory performance modified by DA. The signaling of the DA system, particularly examining the origin of DA-modulated memory, is also discussed. Then, several kinds of memories in which DA plays a critical role, including reward signaling, working memory, and long-term plasticity, as well as memory consolidation, are also described. Finally, memory impairment in some DA-related neurological disorders is also examined.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 4","pages":"558-576"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9150425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of G-Proteins and GPCR-Mediated Signalling in Neuropathophysiology.","authors":"Md Mominur Rahman,&nbsp;Sadia Afsana Mim,&nbsp;Md Rezaul Islam,&nbsp;Nasrin Sultana,&nbsp;Muniruddin Ahmed,&nbsp;Mohammad Amjad Kamal","doi":"10.2174/1871527321666220430142722","DOIUrl":"https://doi.org/10.2174/1871527321666220430142722","url":null,"abstract":"<p><p>G-protein-coupled receptors (GPCRs) are activated by manifold neurotransmitters, and their activation, in turn, evokes slow synaptic transmission. They are profoundly related to numerous psychiatric and neurological disorders such as schizophrenia and Parkinson's disease. The significant malady indications for GPCR modulators demonstrate a change towards obesity, diabetes, and Alzheimer's disease, while other central nervous system disorders persist highly represented. GPR52, GPR6, and GPR8 are recognised as orphan GPCRs, co-exist either with both the dopamine D2 and D1 receptors in neurons of the basal ganglia or with the dopamine D2 receptor alone, and recommend that between these orphan receptors, GPR52 has the maximum potential of being a therapeutic psychiatric receptor. Genetically modified creature models and molecular biological investigations have suggested that these improved GPCRs could be potential therapeutic psychiatric receptors. In this perspective, the role of molecular targets in GPCR-mediated signalling has been discussed that would be novel drug design and discovery options for a scientist to elaborate previous knowledge with modern techniques.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 1","pages":"2-5"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9150443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Endocannabinoid System as a Biomarker for Diagnostic and Therapeutic Applications in Depression and Anxiety.","authors":"Jocelyne Alcaraz-Silva,&nbsp;Daniel Feingold,&nbsp;Gerardo Viana-Torre,&nbsp;Henning Budde,&nbsp;Claudio Imperatori,&nbsp;Sérgio Machado,&nbsp;Eric Murillo-Rodríguez","doi":"10.2174/1871527321666220405114402","DOIUrl":"https://doi.org/10.2174/1871527321666220405114402","url":null,"abstract":"<p><strong>Background: </strong>Depression and anxiety belong to a family of mental disturbances that have increased significantly in recent years. The etiology of both disorders comprises multiple and complex factors, from genetic background to environmental influence. Since depression and anxiety present severe symptoms, they represent a greater clinical burden and greater therapeutic difficulty. Currently, standardized diagnostic procedures for depression and anxiety allow for the addition of further treatments, including psychotherapy and/or pharmacological intervention, with effective outcomes. However, further steps should be considered with regard to consideration of the endocannabinoid system's role in depression and anxiety.</p><p><strong>Objective: </strong>This study aimed to review the evidence from animal research and clinical studies on the role of cannabinoid receptors, the major endocannabinoids -anandamide (AEA) and 2-arachidonoylglycerol (2-AG)- and the enzymes related to the synthesis and degradation of these chemicals as putative biomarkers for diagnostic and therapeutic elements of depression and anxiety.</p><p><strong>Methods: </strong>This review included the online search, identification, and analysis of articles (basic and clinical trials) published in English in PubMed linked to the role of cannabinoid receptors, AEA, 2- AG, and the enzymes associated with the synthesis and degradation of these endocannabinoids in depression and anxiety.</p><p><strong>Results: </strong>The neurobiological relevance of the endocannabinoid system offers genetic or pharmacological manipulation of this system as a potential strategy for the diagnostic and clinical management of mood disorders, including depression and anxiety.</p><p><strong>Conclusion: </strong>Although the described approach in this review is promising, no solid evidence is yet available, and along with additional experiments using animal models that mimic human depression and anxiety, clinical trials are needed to explore the role of the endocannabinoid system's elements as well as the anandamide membrane transporter, none of which have been adequately studied in depression and anxiety.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 3","pages":"417-430"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of Pharmacophore in Designing Anticonvulsant Agents.","authors":"Amol Kale,&nbsp;Rajendra Kakde,&nbsp;Smita Pawar,&nbsp;Vishal Jagtap,&nbsp;Rahul Dorgude","doi":"10.2174/1871527321666220401115529","DOIUrl":"https://doi.org/10.2174/1871527321666220401115529","url":null,"abstract":"<p><p>Drug design is one of the critical aspects of the drug development process. The present review focused on different heterocyclic molecules having anticonvulsant activity with structural diversity and common pharmacophoric features. For the first time (1995), Dimmock and his team introduced specific arrangements of three important pharmacophores for anticonvulsant activity. These pharmacophores include two hydrophobic binding sites and one hydrogen binding site. After a few years (2012), Pandeya modified Dimmock's concept by adding one more pharmacophoric feature as an electron donor in the previously suggested pharmacophoric arrangement of the anticonvulsant. As a result, numerous scientists designed anticonvulsant drugs based on Dimmock's and Pandeya's concept. In addition, marketed anticonvulsant preparation containing Riluzole, Phenobarbital, Progabide, Ralitoline, etc., also holds the suggested pharmacophores by Dimmock and Pandeya's pharmacophoric concept. This review mainly focuses on the compilation of reported scientific literature in the last decade on the pharmacophoric features of different heterocyclic anticonvulsants, which will help develop new anticonvulsants.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 4","pages":"500-511"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9503602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Do Abnormalities in the Cerebrospinal Fluid Impact Neuropsychology with Progressing Age?","authors":"Gargi Joshi,&nbsp;Anna Pick Kiong Ling,&nbsp;Soi Moi Chye,&nbsp;Rhun Yian Koh","doi":"10.2174/1871527321666220408105130","DOIUrl":"https://doi.org/10.2174/1871527321666220408105130","url":null,"abstract":"<p><p>The behavior of an individual changes from neonate to elderly due to the development of the central nervous system (CNS). One of the important components of the CNS is the cerebrospinal fluid (CSF), which bathes the brain and spinal cord. CSF has changing properties throughout life, including composition and volume imbalance. However, a specific age group that shows prevailing abnormality- corresponding behavior remains unclear. The objective of this article is to explore how such changes reflect on one's psychological as well as physical processing. Production of CSF could be affected by many factors, including its flow, absorption, volume, and composition. Prenatally, congenital malformations and infections hold the greatest risk of impacting the child's physical and mental growth. In adolescents, transmission of external substances like alcohol or drugs in the cerebrospinal fluid is known to impact severe mood changes that potentially result in suicide and depression. In the adult working population, the influence of stress levels on CSF composition causes anxiety and sleep disorders. Finally, the reduced production of CSF was found to be associated with memory deficits and Alzheimer's disease in the aging group. From the collected evidence, it can be observed that CSF played an important role in behavioral changes and may be associated with neurodegenerations. By linking the CSF abnormalities to the clinical symptoms at different stages of life, it may provide additional information in the diagnosis of diseases that are associated with neuropsychological changes.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 3","pages":"431-440"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9519347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traumatic Brain Injury in COVID-19 Patients with the Manifestation of Paroxysmal Sympathetic Hyperactivity and Cytokine Storm.","authors":"Zeba Sami,&nbsp;Amaan Javed","doi":"10.2174/1871527321666220420132616","DOIUrl":"https://doi.org/10.2174/1871527321666220420132616","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 6","pages":"786-788"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9534278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temozolomide Resistance: A Multifarious Review on Mechanisms Beyond <i>O</i>-6-Methylguanine-DNA Methyltransferase.","authors":"Vanishree Rao,&nbsp;Gautam Kumar,&nbsp;R J A Vibhavari,&nbsp;Krishnadas Nandakumar,&nbsp;Nanasaheb Thorat,&nbsp;Mallikarjuna Rao Chamallamudi,&nbsp;Nitesh Kumar","doi":"10.2174/1871527321666220404180944","DOIUrl":"https://doi.org/10.2174/1871527321666220404180944","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy with the oral alkylating agent temozolomide still prevails as a linchpin in the therapeutic regimen of glioblastoma alongside radiotherapy. Because of the impoverished prognosis and sparse chemotherapeutic medicaments associated with glioblastoma, the burgeoning resistance to temozolomide has made the whole condition almost irremediable.</p><p><strong>Objective: </strong>The present review highlights the possible mechanisms of drug resistance following chemotherapy with temozolomide.</p><p><strong>Methods: </strong>The review summarizes the recent developments, as published in articles from Scopus, PubMed, and Web of Science search engines.</p><p><strong>Description: </strong>One of the prime resistance mediators, O-6-methylguanine-DNA methyltransferase, upon activation, removes temozolomide-induced methyl adducts bound to DNA and reinstates genomic integrity. In the bargain, neoteric advances in the conception of temozolomide resistance have opened the door to explore several potential mediators like indirect DNA repair systems, efflux mechanisms, epigenetic modulation, microenvironmental influences, and autophagy-apoptosis processes that constantly lead to the failure of chemotherapy.</p><p><strong>Conclusion: </strong>This review sheds light on recent discoveries, proposed theories, and clinical developments in the field of temozolomide resistance to summarize the complex and intriguing involvement of oncobiological pathways.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 6","pages":"817-831"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic and Etiological Similarities in Diabetes Mellitus and Alzheimer's Disease: Antidiabetic Drugs as Optimistic Therapeutics in Alzheimer's Disease.","authors":"Subham Das,&nbsp;Anu K R,&nbsp;Debojyoti Halder,&nbsp;Saleem Akbar,&nbsp;Bahar Ahmed,&nbsp;Alex Joseph","doi":"10.2174/1871527321666220629162229","DOIUrl":"https://doi.org/10.2174/1871527321666220629162229","url":null,"abstract":"BACKGROUND Diabetes mellitus and Alzheimer's disease are two common diseases that majorly affect the elderly population. Patients in both cases are increasing day by day. They are considered two independent diseases, but recent evidence suggests that they have a lot in common. OBJECTIVE In this review we focused on the connection between Alzheimer's disease and diabetes and highlighted the importance of antidiabetic drugs against Alzheimer's disease. METHODS Common pathways such as obesity, vascular diseases, oxidative stress, mitochondrial dysfunction, mutation of ApoE4 gene, and Sirtuin gene were found to manipulate both diseases. Antidiabetic drugs are found to have promising effects on Alzheimer's disease, acting by reducing insulin resistance, neuronal protection, and reducing amyloid-beta plaques. Some anti-diabetic drugs have shown promising results in vivo and in vitro studies. RESULTS No review present focuses on the structural features of the antidiabetic molecules against Alzheimer's disease, their crosslinking pathophysiology, the role of natural bioactive molecules, in silico advancements followed by preclinical and clinical studies, and current advancements. Hence, we concentrated on the factors mentioned in the objectives. CONCLUSION Alzheimer's disease can be considered a form of 'type-3 diabetes,' and repurposing the anti-diabetic drug will open up new paths of research in the field of Alzheimer's disease drug discovery.","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 7","pages":"973-993"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meet the Editorial Board Member","authors":"V. Di Marzo","doi":"10.2174/187152732201220913121030","DOIUrl":"https://doi.org/10.2174/187152732201220913121030","url":null,"abstract":"<jats:sec> <jats:title /> <jats:p /> </jats:sec>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"04 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86779937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}