CNS & neurological disorders drug targets最新文献_第9页

Role of Astrogliosis in the Pathogenesis of Parkinson's Disease: Insights into Astrocytic Nrf2 Pathway as a Potential Therapeutic Target. 星形胶质细胞增生症在帕金森病发病机制中的作用：对星形细胞Nrf2通路作为潜在治疗靶点的见解。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273270473231002104610

Bharat Bhushan, Niraj Kumar Singh

{"title":"Role of Astrogliosis in the Pathogenesis of Parkinson's Disease: Insights into Astrocytic Nrf2 Pathway as a Potential Therapeutic Target.","authors":"Bharat Bhushan, Niraj Kumar Singh","doi":"10.2174/0118715273270473231002104610","DOIUrl":"10.2174/0118715273270473231002104610","url":null,"abstract":"Recently, Parkinson's disease (PD) has become a remarkable burden on families and society with an acceleration of population aging having several pathological hallmarks such as dopaminergic neuronal loss of the substantia nigra pars compacta, α-synucleinopathy, neuroinflammation, autophagy, last but not the least astrogliosis. Astrocyte, star-shaped glial cells perform notable physiological functions in the brain through several molecular and cellular mechanisms including nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. It has been well established that the downregulation of the astrocytic Nrf2 signaling pathway plays a crucial role in the pathogenesis of PD because it is a master regulator of cellular defense mechanism along with a regulator of numerous detoxifying and antioxidant enzymes gene expression. Fascinatingly, upregulation of the astrocytic Nrf2 signaling pathway attenuates the degeneration of nigrostriatal neurons, restores neuronal proliferation, rejuvenates astrocytic functions, and exhibits neuroprotective effects via numerous cellular and molecular mechanisms in the PD-like brain of the experimental animal. Here, we discuss the numerous in-vitro and in-vivo studies that evaluate the neuroprotective potential of the astrocytic Nrf2 signaling pathway against experimentally-induced PD-like manifestation. In conclusion, based on available preclinical reports, it can be assumed that the astrocytic Nrf2 signaling pathway could be an alternative target in the drug discovery process for the prevention, management, and treatment of PD.","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1015-1029"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety and Efficacy of Calcitonin Gene-related Peptide Receptor Antagonists and Selective Serotonin Receptor Agonist in the Management of Migraine: A Systematic Review and Meta-analysis. 降钙素基因相关肽受体拮抗剂和选择性羟色胺受体激动剂治疗偏头痛的安全性和有效性：系统综述与元分析》。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273304677240529062909

Pooja Singh, Rakesh Kumar Ponnada, Ruchika Sharma, Bommaraju Sumadhura, Anoop Kumar, Ashok Kumar Datusalia

{"title":"Safety and Efficacy of Calcitonin Gene-related Peptide Receptor Antagonists and Selective Serotonin Receptor Agonist in the Management of Migraine: A Systematic Review and Meta-analysis.","authors":"Pooja Singh, Rakesh Kumar Ponnada, Ruchika Sharma, Bommaraju Sumadhura, Anoop Kumar, Ashok Kumar Datusalia","doi":"10.2174/0118715273304677240529062909","DOIUrl":"10.2174/0118715273304677240529062909","url":null,"abstract":"Background: Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far.Methods: The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia).Results: The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan.Conclusion: The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1474-1487"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circadian Rhythms and Sleep Disorders Associated to Major Depressive Disorder: Pathophysiology and Therapeutic Opportunities. 与严重抑郁症相关的昼夜节律和睡眠障碍：病理生理学和治疗机会。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273254093231020052002

Luana M Manosso, Luciano A Duarte, Nicoly S Martinello, Gisiane B Mathia, Gislaine Z Réus

{"title":"Circadian Rhythms and Sleep Disorders Associated to Major Depressive Disorder: Pathophysiology and Therapeutic Opportunities.","authors":"Luana M Manosso, Luciano A Duarte, Nicoly S Martinello, Gisiane B Mathia, Gislaine Z Réus","doi":"10.2174/0118715273254093231020052002","DOIUrl":"10.2174/0118715273254093231020052002","url":null,"abstract":"Major depressive disorder (MDD) is a complex mood disorder. While much progress has been made in understanding the pathophysiology of MDD, no single mechanism can explain all facets of this disorder. Several studies show that disturbances in biological rhythms can lead to the development of MDD. Indeed, insomnia or hypersomnia are symptoms included in the MDD diagnostic criteria. Clinical studies and meta-analyses showed a strong relationship between MDD and sleep disorders. Sleep disorder and MDD are associated with activation in the hypothalamicpituitary- adrenal (HPA) axis and inflammation. The increase in inflammatory response can activate the kynurenine pathway, decrease serotonin synthesis, and affect other factors involved in the pathophysiology of neuropsychiatric conditions. Moreover, sleep disorders and MDD can change the gut microbiota and alter the microbiota-gut-brain axis. Thus, this review discusses the relationship between MDD, circadian rhythms, and sleep disorders, describing the potential pathophysiological mechanism shared in these conditions. In addition, therapeutic opportunities based on antiinflammatory, antioxidant, HPA axis regulatory, and synapse-modulating actions are raised. For the article search, we used the PubMed database. Both sleep disorders and changes in biological rhythms have a bidirectional relationship with MDD. Although some pathophysiological mechanisms, including inflammation, changes in the gut microbiota, and decreased neuroplasticity, may be involved in the relationship between sleep, circadian rhythms, and MDD, other mechanisms are not yet well understood. Therapeutic opportunities based on anti-inflammatory, antioxidant, HPA regulatory axis, and synapse modulating actions appear to be promising targets in preventing MDD, circadian rhythm disturbances, and sleep disorders.","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1085-1100"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Landscape of Randomized Clinical Trial Meta-analyses on Statins for Aneurysmal Subarachnoid Hemorrhage: A Scoping Review. 他汀类药物治疗动脉瘤性蛛网膜下腔出血的随机临床试验荟萃分析：范围界定综述。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273270503230928100141

Panagiotis Skouras, Theodosis Kalamatianos, Mariam Markouli, Angelos Karagiannis, Lampis C Stavrinou

{"title":"The Landscape of Randomized Clinical Trial Meta-analyses on Statins for Aneurysmal Subarachnoid Hemorrhage: A Scoping Review.","authors":"Panagiotis Skouras, Theodosis Kalamatianos, Mariam Markouli, Angelos Karagiannis, Lampis C Stavrinou","doi":"10.2174/0118715273270503230928100141","DOIUrl":"10.2174/0118715273270503230928100141","url":null,"abstract":"Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death.Methods: Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen meta-analyses of RCTs, published between 2008 and 2023, were identified.Results: Treatments in included meta-analyses were based on various regimens of simvastatin, pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/ neurological outcome. In contrast, six meta-analyses, showed no such effects.Conclusion: The limitations reported by several meta-analyses, included low patient numbers or disproportionate representation of patients from certain RCTs, differences in drug treatment, patient diagnostic criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their meta-analyses.","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1320-1327"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders. 磷酸二酯酶2及其异构体a作为中枢神经系统疾病的治疗靶点。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/1871527323666230811093126

Sanjay K Metkar, Yuqing Yan, Yue Lu, Jianming Lu, Xiongwei Zhu, Fu Du, Ying Xu

引用次数: 0

Pharmacotherapy in SAH: Clinical Trial Lessons. SAH 的药物治疗：临床试验的启示。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273251761231127095039

Sotirios Apostolakis, Pantelis Stavrinou

{"title":"Pharmacotherapy in SAH: Clinical Trial Lessons.","authors":"Sotirios Apostolakis, Pantelis Stavrinou","doi":"10.2174/0118715273251761231127095039","DOIUrl":"10.2174/0118715273251761231127095039","url":null,"abstract":"Subarachnoid Haemorrhage (SAH) is a medical emergency with potentially devastating outcomes. It is without doubt that over the past decades, there has been a radical change in the approach towards patients with SAH, both in terms of the surgical as well as of the pharmacological treatments offered. The present review aims to outline the principal data regarding the best practice in the pharmacotherapy of SAH, as well as to sum up the emerging evidence from the latest clinical trials. To date, nimodipine is the only evidence-based treatment of vasospasm. However, extensive research is currently underway to identify novel substances with magnesium sulphate, cilostazol, clazosentan and fasudil, demonstrating promising results. Antifibrinolytic therapy could help reduce mortality, and anticoagulants, in spite of their associated hazards, could actually reduce the incidence of delayed cerebral ischemia. The effectiveness of triple-H therapy has been challenged, yet evidence on the optimal regimen is still pending. Statins may benefit some patients by reducing the incidence of vasospasm and delayed ischemic events. As several clinical trials are underway, it is expected that in the years to come, more therapeutic options will be added to the attending physician's armamentarium.","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1308-1319"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications. 抑郁症、焦虑症和神经退行性疾病中的胃肠道问题：关于途径和临床目标影响的系统性综述》。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273289138240306050532

Ian Richard Lucena Andriolo, Bruna Longo, Dayse Machado de Melo, Márcia Maria de Souza, Rui Daniel Prediger, Luisa Mota da Silva

{"title":"Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications.","authors":"Ian Richard Lucena Andriolo, Bruna Longo, Dayse Machado de Melo, Márcia Maria de Souza, Rui Daniel Prediger, Luisa Mota da Silva","doi":"10.2174/0118715273289138240306050532","DOIUrl":"10.2174/0118715273289138240306050532","url":null,"abstract":"Introduction: Multiple illnesses commonly involve both the Central Nervous System (CNS) and the Gastrointestinal Tract (GI) simultaneously. Consistent evidence suggests that neurological disorders impair GI tract function and worsen the symptomatology and pathophysiology of digestive disorders. On the other hand, it has been proposed that early functional changes in the GI tract contribute to the genesis of several CNS illnesses. Additionally, the role played by the gut in these diseases can be seen as a paradigm for how the gut and the brain interact.Methods: We mentioned significant GI symptoms and discussed how the GI tract affects central nervous system illnesses, including depression, anxiety, Alzheimer's disease, and Parkinson's disease in this study. We also explored potential pathophysiological underpinnings and novel targets for the creation of future therapies targeted at gut-brain connections.Results & discussion: In this situation, modulating the gut microbiota through the administration of fecal microbiota transplants or probiotics may represent a new therapeutic option for this population, not only to treat GI problems but also behavioral problems, given the role that dysbiosis and leaky gut play in many neurological disorders.Conclusion: Accurate diagnosis and treatment of co-existing illnesses also require coordination between psychiatrists, neurologists, gastroenterologists, and other specialties, as well as a thorough history and thorough physical examination.","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1371-1391"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential Neuroprotective Role of Neurotrophin in Traumatic Brain Injury. 神经营养素在创伤性脑损伤中的潜在神经保护作用

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273289222231219094225

Rei Shian Yap, Jaya Kumar, Seong Lin Teoh

{"title":"Potential Neuroprotective Role of Neurotrophin in Traumatic Brain Injury.","authors":"Rei Shian Yap, Jaya Kumar, Seong Lin Teoh","doi":"10.2174/0118715273289222231219094225","DOIUrl":"10.2174/0118715273289222231219094225","url":null,"abstract":"Traumatic brain injury (TBI) is a major global health issue that affects millions of people every year. It is caused by any form of external force, resulting in temporary or permanent impairments in the brain. The pathophysiological process following TBI usually involves excitotoxicity, mitochondrial dysfunction, oxidative stress, inflammation, ischemia, and apoptotic cell death. It is challenging to find treatment for TBI due to its heterogeneous nature, and no therapeutic interventions have been approved thus far. Neurotrophins may represent an alternative approach for TBI treatment because they influence various functional activities in the brain. The present review highlights recent studies on neurotrophins shown to possess neuroprotective roles in TBI. Neurotrophins, specifically brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have demonstrated reduced neuronal death, alleviated neuroinflammatory responses and improved neurological functions following TBI via their immunomodulatory, anti-inflammatory and antioxidant properties. Further studies are required to ensure the efficacy and safety of neurotrophins to be used as TBI treatment in clinical settings.","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1189-1202"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of Psychological Stress on Multiple Sclerosis via HPA Axis-mediated Modulation of Natural Killer T Cell Activity. 心理压力通过 HPA 轴介导的自然杀伤 T 细胞活性调节对多发性硬化症的影响

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273315953240528075542

Yafei Gao, Wenying Liu, Paiyu Liu, Min Li, Bing Ni

引用次数: 0

Designing and Formulation of Nanocarriers for "Alzheimer's and Parkinson's" Early Detection and Therapy. 设计和制备纳米载体，用于 "阿尔茨海默氏症和帕金森氏症 "的早期检测和治疗。

CNS & neurological disorders drug targets Pub Date : 2024-01-01 DOI: 10.2174/0118715273297024240201055550

Jakleen Abujamai, Rukhsana Satar, Shakeel Ahmed Ansari

引用次数: 0