CNS & neurological disorders drug targets最新文献

{"title":"Oxidative Stress and the Role of Immune Cells in Alzheimer's Disease: Therapeutic Implications and Future Perspectives.","authors":"Nidhi Puranik, Minseok Song","doi":"10.2174/0118715273355336250226055826","DOIUrl":"https://doi.org/10.2174/0118715273355336250226055826","url":null,"abstract":"<p><p>The most common neurodegenerative illness and leading cause of death in the world is Alzheimer's disease (AD), which is extremely expensive to treat. None of the AD treatments that are currently in the market with approval have any effect on disease progression. However, numerous clinical studies aimed at reducing amyloid beta (Aβ) plaque development, boosting Aβ clearance, or reducing neurofibrillary tangle (NFT) failed or had conflicting results. As oxidative stress (OS), mitochondrial dysfunction, and chronic neuroinflammation are implicated in numerous interconnected vicious cascades, research has revealed new therapeutic targets, including enhancing mitochondrial bioenergetics and quality control, reducing oxidative stress, or modulating neuroinflammatory pathways. This review examines the role of oxidative stress (OS), mitochondrial dysfunction, neuroinflammation, and the interplay between peripheral and central immune systems in the pathogenesis of AD. We highlight how OS and immune dysregulation drive chronic neuroinflammation, exacerbating AD progression. Immune cells and inflammatory molecules emerge as critical players in disease pathology. Overall, this review concludes that targeting OS and immune system crosstalk represents promising therapeutic strategies for mitigating AD progression, providing a foundation for future interventions.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671990","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}

{"title":"Lithium Chloride Rescues Dopaminergic Neurons in a Parkinson's Disease Rat Model Challenged with Rotenone.","authors":"Eman Allam, Sary Khalil Abdel Ghafar, Manal Hussein, Ahmed Al-Emam, Khaled Radad","doi":"10.2174/0118715273365449250224090655","DOIUrl":"https://doi.org/10.2174/0118715273365449250224090655","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease, the second most common neurodegenerative disease, is still lacking an effective treatment that can stop dopaminergic cell loss in substantia nigra and alter disease progression.</p><p><strong>Objective: </strong>The present study aimed to investigate the neuroprotective efficacy of lithium chloride in a rotenone-induced rat model of Parkinson's disease.</p><p><strong>Methods: </strong>Forty male Sprague Dawley rats were assigned into 4 groups: control, rotenone-, rotenone and lithium chloride- and lithium chloride-treated groups. Rotenone (2 mg/kg b.w.) and lithium chloride (60 mg/kg b.w.) were, respectively, administered subcutaneously and orally five times a week for 5 weeks. At the end of each treatment, the neuroprotective efficacy of lithium chloride against rotenone-induced derangements was evaluated by some behavioral tests, biochemical analysis, gel electrophoresis, histopathology, and immunohistochemistry.</p><p><strong>Results: </strong>Rotenone significantly resulted in neurobehavioral deficits, gastrointestinal dysfunction, decreased activities of catalase and superoxide dismutase, depleted glutathione, and increased levels of malondialdehyde. It also caused DNA fragmentation and loss of dopaminergic neurons in substantia nigra and decreased striatal tyrosine hydroxylase staining intensity. Concomitant treatment of rats with rotenone and lithium chloride significantly improved behavioral impairment and markedly alleviated gastrointestinal dysfunction. It also increased catalase activity and decreased malondialdehyde levels, indicating antioxidant effects. Moreover, it decreased DNA fragmentation, rescued dopaminergic neurons, and increased tyrosine hydroxylase immunoreactivity in the striatum compared to the rotenone-treated group.</p><p><strong>Conclusion: </strong>Lithium chloride rescued dopaminergic neurons in a rotenone model of PD, possibly through the improvement of behavioral deficits, decreasing oxidative stress, and reducing DNA damage.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671987","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}

{"title":"Identification of Known Flavonoids of Ficus carica L. as Aldose Reductase Inhibitors in Sciatic Nerve of Diabetic Neuropathy-induced Rats through Bioinformatics and Proteomics Analysis.","authors":"Dureshahwar Khan, Hemant D Une, Mubashir Mohammed, Jaiprakash N Sangshetti, Sanjay N Harke, Manoj Damale, Jitendra B Naik","doi":"10.2174/0118715273322121250124065659","DOIUrl":"https://doi.org/10.2174/0118715273322121250124065659","url":null,"abstract":"<p><strong>Introduction: </strong>The polyol pathway is responsible for the metabolism of almost one-third of the total glucose in people with chronic diabetes. Moreover, it causes complications in organs that rely on aldose reductase (AR) as an enzyme. The purpose of this research was to examine the in vitro and in vivo effects of a flavonoid-rich ethyl acetate fraction of a methanolic extract of Ficus carica Lam. leaves (FCEA) on the aldose reductase gene AKR1B1. The complicated relation of AR for target confirmation and analysis of the flavonoids of FCEA, quercetin, kaempferol, and chrysin was explored by building a flavonoid-protein complex network utilizing GeneCards®, String, and Cytoscape Networking.</p><p><strong>Method: </strong>The examination of ADMET was carried out after docking on the active sites of AR. By the binding and scoring abilities, the analysis was carried out. The ADMET characteristics demonstrated that these flavonoids had excellent solubility, absorption, and oral bioavailability, and the results demonstrate that they have potential. An additional in-vivo investigation was conducted on rats using a model induced by streptozotocin (STZ). Hence, upon induction, the rats' sciatic nerves were removed and prepared for an RT-PCR analysis of the AKR1B1 gene.</p><p><strong>Result: </strong>Compared to the diabetic normal group and the metformin group, rats treated with FCEA had lower levels of messenger RNA and AKR1B1 gene expression.</p><p><strong>Conclusion: </strong>This proves that FCEA has effectively blocked AR. It is highly likely to suggest FCEA as a potent aldose reductase inhibitor, as it considerably reduces the mRNA level of AKR1B1 gene expression in the sciatic nerve of sick rats, according to a combined bioinformatics prediction and RT-PCR analysis.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607556","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}

{"title":"Dopamine Depletion in Parkinson's Disease and Therapeutic Options.","authors":"Hussaini Adam, Subash C B Gopinath, Tijjani Adam, Evan T Salim, Makram A Fakhri","doi":"10.2174/0118715273366223250302092948","DOIUrl":"https://doi.org/10.2174/0118715273366223250302092948","url":null,"abstract":"","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588420","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}

{"title":"Chlorogenic Acid as a Neuroprotective Agent: Enhancing Plasticity and Promoting Brain Health and Functional Reserve.","authors":"Elizabeth Hernández-Echeagaray, Rubén Vázquez-Roque, Julio Cesar Morales-Medina, Francisco M Torres-Cruz, Elibeth Monroy, Gulmaro Galindo-Paredes, Gabriel Gutiérrez-Ospina, Gonzalo Flores","doi":"10.2174/0118715273339375250116042441","DOIUrl":"https://doi.org/10.2174/0118715273339375250116042441","url":null,"abstract":"<p><strong>Introduction: </strong>Functional reserve, the process that warrants the brain to have resources to maintain key functions and processes when facing neurodegeneration, may be strengthened in nominally healthy subjects by measures that prompt neural plasticity throughout life.</p><p><strong>Method: </strong>In this work, we administered Chlorogenic Acid (CGA) to evaluate its ability to promote functional morphological plasticity in the frontal cortical-striatal circuit of healthy mice, a pathway exposed constantly to oxidative challenges, excitotoxicity, and neuroinflammation. The magnitude of neural plasticity was estimated by assessing spontaneous motor behavior (open field), the relative magnitude of neuronal activation (number of c-Fos positive neurons), dendritic remodeling (Golgi- Cox impregnation), the availability of Brain-Derived Neurotrophic Factor (BDNF) (semiquantitative Western blotting), and lipid peroxidation (TBARS assay) in CGA- or vehicle-administered C57BL/6 male mice.</p><p><strong>Results: </strong>CGA administration increased c-Fos in the Dorsal striatum (Ds), changed the availability of BDNF and Pro-BDNF in the Frontal Cortex (FC) and DS, induced dendritic remodeling in FC and DS neurons, and reduced FC and DS lipid peroxidation without affecting motor performance or the availability of TrkB receptor isoforms.</p><p><strong>Conclusion: </strong>Our findings suggest that CGA increases functional reserve by promoting neuronal plasticity in healthy male mice. Future research should determine whether these additional resources indeed protect against neurodegeneration.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525581","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}

{"title":"Fluoride-induced Neurodevelopmental Toxicity- AMPK as a Possible Target.","authors":"Tejas Ahuja, Farmiza Begum, Fathima Beegum, Gautam Kumar, Nitesh Kumar, Rekha R Shenoy","doi":"10.2174/0118715273300345250206084817","DOIUrl":"https://doi.org/10.2174/0118715273300345250206084817","url":null,"abstract":"<p><p>Inorganic fluoride is widely used in dental practices to treat problems like dental caries and prevent bone-related issues. Exposure to excess amounts of fluoride both through drinking water or other sources impairs vital functions of the body and can prove to be toxic, especially for the central nervous system. Sodium fluoride (NaF) crosses the blood-brain barrier in early developmental stages and causes impairments related to learning and memory, anxiety, decreased locomotor ability, and in some cases, depression-like behaviour, especially in children. Major mechanisms involved in this toxicity include reduction in levels of nicotinic and muscarinic receptors, autophagy, and apoptosis in neurons, decreased glucose consumption, inhibition of enzymes involved in the generation of energy and transmission of the synapse, mitochondrial dysfunction, and increased oxidative stress leading to inflammation and neuronal cell death. Out of all these, an increase in oxidative stress was reported to be one of the main mechanisms of fluoride-induced neurotoxicity. Based on these inferences, various natural compounds having antioxidant properties, like curcumin, aloe vera, quercetin, epigallocatechin gallate, etc. have been studied for their protective role in sodium fluoride-induced neurotoxicity. Involvement of other pathways like Nrf2/Keap pathways, SIRT3, etc., have warranted a need for further detailed study to identify other potential therapeutic targets like AMPK to prevent/treat fluoride-induced neurotoxicity. The present review captures fluoride, its role in neurodevelopment, and mechanisms & pathways involved by which fluoride can hurt neurodevelopment & how AMPK can be a possible therapeutic target.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495050","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}

{"title":"Genetic Predisposition and Severity of Eating Disorders- A Review.","authors":"Md Harun Rashid, Neha Deora, Shashidhar Ravindra Kolur, Suttur S Malini, Priyankar Sen","doi":"10.2174/0118715273372810250214054917","DOIUrl":"https://doi.org/10.2174/0118715273372810250214054917","url":null,"abstract":"<p><p>Eating disorders (EDs) are multifaceted psychiatric conditions with significant genetic, psychological, and environmental components. This review provides a comprehensive analysis of the genetic underpinnings and key molecular pathways contributing to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Genetic studies, particularly genome-wide association studies (GWAS), have identified key loci associated with ED susceptibility, with heritability estimates for these disorders ranging between 48% and 74%. Among the critical genes explored, the Agouti-related protein (AGRP), ghrelin (GHRL), and brain-derived neurotrophic factor (BDNF) pathways emerge as pivotal regulators of appetite control, energy balance, and reward systems, offering insights into ED etiology. These pathways are modulated by environmental factors and often dysregulated in individuals with EDs, linking abnormal eating behaviors to disturbances in neurobiological functions. EDs also show a strong association with comorbid psychiatric disorders, such as depression and anxiety, and pose significant physical health risks, including cardiovascular disease and metabolic disturbances. Exploring the intricate genetic and neurobiological mechanisms underlying eating disorders (EDs) paves the way for more effective prevention, early detection, and tailored treatment strategies. This review highlights the potential of utilizing genetic insights to enhance diagnostic and intervention strategies, ultimately leading to better outcomes for individuals impacted by eating disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484731","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}

{"title":"Internet of Medical Things (IoMT) for Alzheimer Patient's Outcome.","authors":"Thangavel Lakshmipriya, Subash C B Gopinath","doi":"10.2174/0118715273371149250218081425","DOIUrl":"https://doi.org/10.2174/0118715273371149250218081425","url":null,"abstract":"<p><p>The Internet of Medical Things (IoMT) is a network system that connects devices with medical and healthcare for the ultimate aim of collecting, transmitting, and analyzing the acquired data in the presence of the internet. A wide range of equipment and monitoring systems have been generated with IoMT, and they permit real-time monitoring, sharing the data, analysis, patient care, and for efficient operation. At the advanced level, it is highly facilitated with remote patient digital monitoring and telemedicine. IoMT has a significant potential to enhance the care of Alzheimer's disease patients to overcome issues with a progressive neurological condition, memory loss, cognition, and behavior. This study aims to bring the potential of the Internet of Things (IoT) to be implemented in the Internet of Medical Things (IoMT), with a special focus on Alzheimer's disease patients.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484732","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}

{"title":"Serotonergic Dynamics in Autism Spectrum Disorder: Unraveling the Intricate Connection.","authors":"Abhishek Chander, Jeetesh Sharma, Shushank Mahajan, Sanchit Dhankhar, Samrat Chauhan, Monika Saini, Sanjana Mehta","doi":"10.2174/0118715273378214250213114328","DOIUrl":"https://doi.org/10.2174/0118715273378214250213114328","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) constitutes a group of neurodevelopmental disorders characterized by impairments in verbal and nonverbal communication skills, social interactions, and stereotypes of behavior, with an estimated frequency of 1.2% of children throughout the world. The lack of specific treatments or molecular biomarkers underscores the complexities of ASD as a nonunified clinical entity. Comorbid medical conditions are particularly associated with gastrointestinal issues that may suggest potential interactions between the brain and gut. This review suggests that serotonin plays a significant role in the enteric and central nervous systems in relation to ASD. The modulatory role of serotonin in the enteric nervous system is examined in relation to the pathophysiology of ASD in order to shed light on prospective biomarkers and therapeutic targets that could increase the precision of diagnosis and treatment.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461233","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}

{"title":"A Review on Nanotechnology based In Situ Gelling System as a Reliable Weapon for Targeting Alzheimer's Disease via Intranasal Route.","authors":"Priyanka Deorankar, Vahid Vikram Minglani, Bhupendra G Prajapati, Meenakshi B Patel","doi":"10.2174/0118715273335978250127070434","DOIUrl":"https://doi.org/10.2174/0118715273335978250127070434","url":null,"abstract":"<p><p>A recent World Health Organization report claims that along with the growing world population and emerging life prospects, the prevalence of neurological disorders is also increasing. Out of all neurological disorders, Alzheimer's disease is the most widespread and alarming concern. The disease poses significant therapeutic challenges due to the blood-brain barrier's restrictiveness and the lack of effective drug delivery systems. The olfactory and trigeminal nerves have direct access to the brain, therefore, intranasal drug delivery can be a promising route for the direct delivery of anti-Alzheimer's drugs. Despite this advantage, brain targeting is limited through this route due to mucociliary clearance. Thus, in situ, nanotechnology offers a transformative approach by leveraging the intranasal route to directly target the central nervous system. This comprehensive review discusses recent advancements, mechanisms, and applications of in situ nanotechnology in Alzheimer's disease therapeutics, highlighting its potential to enhance drug delivery efficiency, improve bioavailability, and mitigate the progression of this debilitating condition. The importance of intranasal drug delivery has been emphasized in this review, along with the clear benefits of in situ lipid- based nanotechnology for the efficient delivery of medication in targeting Alzheimer's disease.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451187","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}