Central nervous system agents in medicinal chemistry最新文献

{"title":"Role of Morin & Alpha-Lipoic Acid in Diabetic Neuropathic Pain.","authors":"Ankita Wal, Pranay Wal, Gagandeep Singh Basra, Ritu Rani Yadav, Srilekha Das Nag, Shiva Mishra, Amin Gasmi","doi":"10.2174/0118715249352790250711092129","DOIUrl":"https://doi.org/10.2174/0118715249352790250711092129","url":null,"abstract":"<p><p>Recent studies have shown that plant-derived flavonoids may be useful in the treatment of diabetes. Plants in the Moraceae family are commonly known to contain the bioflavonoid morin. Its pharmacological properties include anti-inflammatory, anti-tumor, anti-diabetic, cardioprotective, neuroprotective, and nephroprotective properties. An organic dithiol molecule called alpha-lipoic acid is essential to mitochondrial bioenergetic functions. Its antioxidant properties have led to significant research in the treatment of diabetic conditions. Diabetic neuropathic pain is associated with poor glucose regulation and metabolic abnormalities, specifically oxidative stress (OS) and inflammation. Many mediators and signaling pathways play a crucial role in the development and pathogenesis of diabetic neuropathic pain, including the polyol pathway, advanced glycation end products, glutamate pathway, trophic factors, activation of channels, inflammation, and OS. Morin is useful in controlling blood sugar levels and lowering the problems associated with diabetes, according to studies conducted in a variety of in vitro and in vivo studies. Alpha-lipoic acid (ALA) is a naturally occurring chemical that is necessary for the function of specific enzymes involved in mitochondrial and oxidative metabolism. Dihydrolipoic acid (DHLA), the reduced form of ALA, is thought to have a variety of biological activities, including the reduction of oxidized forms of other agents, including vitamin E and C, metal chelation, and modulation of signal transduction of several pathways (insulin). With its antioxidant properties and ability to scavenge reactive oxygen species, ALA may be able to inhibit the oxidative stress-inflammation pathways that are triggered in diabetic neuropathy. Thus, in this paper, we studied the impact of dietary flavonoid morin and alpha lipoic acid on the molecular mechanism causing major diabetic problems.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746528","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":"Synthesis, Computational Studies of New Chalcone Derivatives as Anxiolytics and Skeletal Muscle Relaxants.","authors":"Priti Tiwari, Sushil Kumar, Jatin Kishore Sharma, Akhlesh Kumari","doi":"10.2174/0118715249384074250709074253","DOIUrl":"https://doi.org/10.2174/0118715249384074250709074253","url":null,"abstract":"<p><strong>Introduction: </strong>Chalcone derivatives are known for their diverse biological activities, including anxiolytic and skeletal muscle relaxant properties. Recent studies indicate that structural modifications can enhance their therapeutic effectiveness. This study aimed to synthesize and biologically evaluate novel chalcone derivatives, investigating their structure-activity relationship through computational studies and assessing their pharmacological potential.</p><p><strong>Methods: </strong>Five chalcone derivatives (P1-P5) were synthesized via Claisen-Schmidt condensation and characterized using infrared spectroscopy (IR) and nuclear magnetic resonance (NMR) spectroscopy. Their physicochemical and pharmacokinetic profiles were analyzed via SWISS ADME, confirming drug-likeness. Biological assessments, including the Elevated Plus Maze (EPM), Open Field Test (OFT), Hole Board Test (HBT), and Rotarod Test, were conducted to evaluate anxiolytic and muscle-relaxant activities.</p><p><strong>Results: </strong>The synthesized chalcones exhibited yields of 60%-75% and complied with Lipinski's rule, showing no violations. Among the tested compounds, P2 demonstrated the highest anxiolytic activity, as evidenced by increased exploratory behaviour in EPM, OFT, and HBT. P1 exhibited the strongest skeletal muscle relaxant effect in the Rotarod Test, comparable to diazepam.</p><p><strong>Discussion: </strong>The study findings suggest that these chalcone derivatives may serve as promising candidates for anxiolytic and muscle-relaxant therapy. Computational analysis supports their pharmacokinetic suitability. Further research is necessary to explore their mechanisms and potential clinical applications.</p><p><strong>Conclusion: </strong>Chalcone derivatives (P1-P5) were successfully synthesized and studied. They showed strong effects for reducing anxiety and relaxing muscles, making them worthy of further research.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676847","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":"Computational Design of Drugs for Epilepsy using a Novel Guided Evolutionary Algorithm for Enhanced Blood Brain Barrier Permeability.","authors":"Sekhar Talluri","doi":"10.2174/0118715249385792250709073502","DOIUrl":"https://doi.org/10.2174/0118715249385792250709073502","url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy is a common disorder of the Central Nervous System (CNS). The rational design of small-molecule drugs for disorders of the CNS is a difficult process because the majority of small molecules are unable to cross the Blood-Brain-Barrier. An efficient method for the design of inhibitors that have high permeability through the Blood-Brain-Barrier has the potential for application in drug design for CNS disorders such as Addiction, Alzheimer's disease, Bipolar disorder, Depression, Epilepsy, Gliomas, and Tuberculous meningitis.</p><p><strong>Method: </strong>Supervised learning was used to model the Blood-Brain-Barrier permeability of drugs like small organic molecules. This information was utilized to guide an evolutionary algorithm for the design of inhibitors with increased affinity for the target as well as higher Blood-Brain-Barrier permeability.</p><p><strong>Results: </strong>The ligands designed with guided evolution were predicted to have higher binding affinity for the target as well as higher permeability across the Blood-Brain-Barrier compared to an evolutionary algorithm without the guidance. The guided evolutionary method was applied to design a set of drug-like ligands that were predicted to bind to GABA-T with high affinity, to be BBB permeable, and to be chemically synthesizable.</p><p><strong>Discussion: </strong>Despite the availability of several drugs that are approved for the treatment of epilepsy, there are many cases that do not respond to available drugs or experience adverse effects. The novel ligands designed as part of this work have the potential to address the limitations of available drugs.</p><p><strong>Conclusion: </strong>Guided evolution is an efficient computational approach for the design of CNS drugs. The de novo design of drugs by application of the guided evolution algorithm, developed as part of this work, has resulted in the generation of ligands that are potential drugs for the cure of epilepsy. However, the effectiveness of these drugs for the cure of epilepsy has to be validated experimentally.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638905","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 Mini-Review on Unlocking Cognitive Enhancement: An Innovative Strategy for Optimal Brain Functions.","authors":"Akash Vikal, Rashmi Maurya, Brij Bihari Patel, Preeti Patel, Manish Kumar, Balak Das Kurmi","doi":"10.2174/0118715249357704250702140026","DOIUrl":"https://doi.org/10.2174/0118715249357704250702140026","url":null,"abstract":"<p><p>Cognitive enhancement, aimed at improving or preserving memory, attention, and executive functions, has gained significant interest from both the scientific community and the public. This review explores various strategies for enhancing cognitive function, including natural compounds, synthetic enhancers, and behavioural approaches. Natural compounds like curcumin, <i>Ginkgo biloba, Panax ginseng</i>, and <i>Rhodiola rosea</i> are examined for their cognitive benefits, with ongoing research on their mechanisms and potential nanoformulation-based drug delivery. Synthetic enhancers such as Modafinil, Piracetam, Methylphenidate, and Noopept show promise in improving cognitive functions. Additionally, substances influencing brain metabolism, like Creatine and Coenzyme Q10, are discussed. Behavioural interventions, including sleep optimization, meditation, and physical exercise, are evaluated for their cognitive-enhancing effects. Noninvasive brain stimulation techniques, such as TMS and tDCS, along with innovative methods like whole-body vibration and brain-machine interfaces, are also explored. The review emphasizes the complex interplay of these strategies and the need for continued research to fully exploit their potential. By highlighting natural compounds, synthetic drugs, and behavioural approaches, the review advocates for a multifaceted approach to cognitive enhancement and calls for more detailed and longitudinal studies to understand their long-term benefits and mechanisms.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638904","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":"The Biochemical Effects of Resveratrol Intake on the Neurobehavioral Aspects of Autism Spectrum Disorders: A Systematic Review.","authors":"Masoud Nikfarjam, Saeid Heidari-Soureshjani, Sahar Rostamian, Karamali Kasiri","doi":"10.2174/0118715249387274250521054238","DOIUrl":"https://doi.org/10.2174/0118715249387274250521054238","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by various neurobehavioral impairments. This study aims to review the preventive and therapeutic effects of Resveratrol (RSV) against ASD during various stages of life, specifically focusing on its influence on behavioral and neurodevelopmental biochemical mechanisms.</p><p><strong>Methods: </strong>On December 6, 2024, a comprehensive electronic search was conducted across several high-coverage databases, including Web of Science, Scopus, PubMed/MEDLINE, Embase, and the Cochrane Library. The most important data were extracted and reviewed after screening the publications based on our inclusion and exclusion criteria.</p><p><strong>Results: </strong>RSV alleviates autistic-like social behaviors by promoting social interaction and mitigating repetitive behaviors, anxiety, and symptoms resembling depression. RSV influences chemokine receptor expression, diminishes pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ), and regulates mitochondrial function by reducing nitrosative stress and thiobarbituric acid reactive substances (TBARS) levels, while also increasing antioxidant markers like glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) in the brain. Additionally, it enhances neuronal organization, increases the proportions of interneurons (SOM+, PV+, CB+), and restores the integrity of the hippocampus. Moreover, RSV modulates epigenetic pathways, such as estrogen receptorbeta (ERβ) activation and sirtuin 1 (Sirt1) expression, counteracts learning, memory, and locomotor activity deficits, and normalizes cortical oscillations. It also potentially modulated gutbrain- axis dysregulation and neurotransmitters.</p><p><strong>Conclusion: </strong>RSV has shown promising effects on ASD, primarily through its influence on behavioral, neuromolecular, and neurodevelopmental mechanisms.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328126","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":"Evaluation of Anti-epileptic Activity of Cyanthillium cinereum (L.) H. Rob. Leaves in the Experimental Pentylenetetrazole-induced Epileptic Model.","authors":"Kundan Singh Bora, Kanupriya Kumari","doi":"10.2174/0118715249352799250512015642","DOIUrl":"https://doi.org/10.2174/0118715249352799250512015642","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a common and frequently devastating disorder affecting millions of people. According to a recent survey, 1-2% of the Indian population suffers from major mental disorders and 5% suffers from minor mental disorders. Epilepsy is among those mental disorders that affect 30 million people worldwide. Currently, the treatment of epilepsy involves agents which modulate sodium-ion channels, enhance GABAergic transmission, and agents with multiple modes of action. Various classes of synthetic drugs are used to treat epilepsy, but these drugs are often challenged due to their unwanted side effects. Medicinal plants have been a part of human society which combating diseases from the dawn of civilization. The plant Cyanthillium cinereum (L.) H. Rob. is mainly found in the Himalayas from Kashmir to Nepal at an altitude of 8000 m. Decoction of this plant is traditionally used as an anti-cancer, anti-malarial, anti-epileptic, and in neurosis and skin diseases.</p><p><strong>Objectives: </strong>The present study investigated the anti-epileptic activity of Cyanthillium cinereum leaves against pentylenetetrazole (PTZ)-induced epileptic model in mice.</p><p><strong>Methods: </strong>Plant extracts were prepared using solvents in increasing polarity viz., petroleum ether, chloroform, ethanol, and water, using a Soxhlet apparatus. The bio-active extract was characterized using FTIR and GC techniques. In vivo antioxidants like GSH and SOD level, oxidative stress markers- MDA and hemoglobin and platelet count were also estimated in the animal brain.</p><p><strong>Results: </strong>Amongst all extracts tested, only ethanol extract of Cyanthillium cinereum significantly (p<0.05) inhibited generalized tonic-clonic seizures in PTZ-induced epilepsy in mice in a dose (100 or 200 mg/kg., p.o.) dependent manner. The dose of 200 mg/kg of extract exhibited the most significant effect. It is also found that treatment with ethanol extract on PTZ-induced epilepsy in mice significantly (p<0.05) reduces the duration of convulsion and delays the onset of clonic convulsion.</p><p><strong>Conclusion: </strong>The present findings suggest that the high amounts of phenols and flavonoids in the ethanol extract could be responsible for the anti-epileptic effect. Moreover, the ethanol extract also restored GSH, SOD and hemoglobin and platelet level and decreased oxidative marker- MDA content in the mice brain.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188704","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":"The Role of Novel Biomarkers in the Early Management of Peripheral Diabetic Neuropathy.","authors":"Jyoshna Rani Dash, Gurudutta Pattnaik, Gangadhar Pradhan, Choudhury Pratyush Kumar Baral, Biswajit Behera, Goutam Ghosh, Goutam Rath, Biswakanth Kar","doi":"10.2174/0118715249358465250522173332","DOIUrl":"https://doi.org/10.2174/0118715249358465250522173332","url":null,"abstract":"<p><p>Diabetes can frequently result in peripheral diabetic neuropathy (PDN), a lifethreatening illness that impairs the motor and sensory abilities of peripheral nerves. Prompt identification and management of peripheral neuropathy are essential to avert permanent nerve impairment and enhance the well-being of affected individuals. In addition, axonal degeneration is usually detected at a late stage of the disease and serves as a basis for developing modern diagnostic techniques. Novel biomarkers that can detect PDN early and track its development are thus required. In this review, we highlight the most recent developments in identifying and verifying putative biomarkers for PDN, emphasizing their connections to the pathophysiology and clinical presentations of the illness. The challenges and opportunities for developing biomarker-based diagnostic and therapeutic strategies for PDN are also discussed. It is suggested that biomarkers help predict the response and outcome of PDN treatments, such as poly (ADP-ribose) polymerase inhibitors and regenerative medicine.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188705","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":"Cerebroprotective Potential of Androgen Receptors in Ischemic Postconditioning against Cerebral Ischemia/Reperfusion-Induced Neurodegenerative Changes.","authors":"Prabhat Singh, Surbhi Gupta, Bhupesh Sharma, Lubhan Singh, Rani Bansal, Mamta Gupta","doi":"10.2174/0118715249354207250429041513","DOIUrl":"https://doi.org/10.2174/0118715249354207250429041513","url":null,"abstract":"<p><strong>Background and objective: </strong>In stroke, reperfusion of blood to the cerebral ischemic area following sustained ischemia further exacerbates tissue damage, identified as cerebral ischemia and reperfusion (I/R) insult. Ischemic post-conditioning (IPoC) appears to offer benefits against I/R injury. The cascade of androgen receptors (ARs) has a vital role in cerebral stroke; however, its neurodefensive function in IPoC is unclear. This investigation aimed to explore the involvement of ARs in IPoC in cerebral I/R insult in rats.</p><p><strong>Methods: </strong>Global cerebral ischemia/reperfusion (GCI/R) insult in experimental animals was provoked by 10 minutes of obstruction of the bilateral carotid arteries after reperfusion for 24 hours. IPoC was carried out by providing a triad of I/R insults with a gap of 10 minutes of GCI after 24 hours of reperfusion. Lateral push, inclined beam, rota rod, hanging wire, and Morris-water maze experimentations were conducted on animals to determine motor control and cognitive functions (learning and memory). Cerebral oxidative damage markers (raised lipid peroxidation and reduced glutathione levels), acetylcholinesterase (AChE) activity, inflammatory indicators (interleukin-6, interleukin-10, tumor necrosis factor-α, and myeloperoxidase), infarction, and histopathological alterations were also assessed.</p><p><strong>Results: </strong>Animals with I/R exhibited reduced motor function and memory along with raised cerebral oxidative damage, AChE activity, inflammation, infarction, and histopathological alterations. IPoC after ischemic events recuperated the damaging outcomes of I/R insult. 60 minutes before cerebral ischemia, pretreatment with testosterone mimicked the neurodefensive outcomes of IPoC. However, neuroprotective outcomes developed by IPoC were diminished by flutamide (ARs antagonist) pretreatment.</p><p><strong>Conclusion: </strong>IPoC may offer neuroprotective outcomes in I/R insult by modulation of ARmediated pathway.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082761","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":"Unveiling the Pharmacological Effects of Ginkgo biloba: Clinical Relevance and Applications.","authors":"Deepshi Arora, Yugam Taneja, Aakriti Saini, Bhawna Chopra, Manish Kumar, Shailendra Bhatt, Ajmer S Grewal, Ashwani K Dhingra","doi":"10.2174/0118715249362016250401085542","DOIUrl":"https://doi.org/10.2174/0118715249362016250401085542","url":null,"abstract":"<p><p>The consumption and utilization of Ginkgo biloba leaves and seeds in traditional herbal treatments have left an indelible mark. Their rich chemical makeup and remarkable pharmacological effects, particularly in the form of EGb761 leaf extracts, have captivated researchers seeking novel treatments for degenerative nerve illnesses like Alzheimer's disease. However, the story of Ginkgo biloba doesn't end there. The Ginkgo biloba seeds, which were once highly regarded as sustenance and medicine but are often overlooked, hold ancient wisdom that awaits discovery and understanding, also, it is advised to consume one to two seeds per day because of the ginkgo toxin side effect. Traditional Chinese medicine has harnessed its potential to combat intestinal tract worm infections, pyogenic skin diseases, enuresis, asthma, cough, and more, owing to its abundant reserves of carbs, protein, fat, and polyphenols. Moreover, recent studies have emerged, suggesting their neuroprotective properties. Fostering awareness and encouraging the consumption of Ginkgo biloba seeds thus becomes paramount. As we embark on a quest to delve into the depths of Ginkgo biloba seeds, this comprehensive review aims to shed light on their key components, bioactivities, processing techniques, and the latest insights into their pharmacological actions. By embracing a holistic understanding of Ginkgo biloba seeds, we lay the foundation for their scientific advancement and the development of this remarkable edible seed. Furthermore, it is essential to acknowledge that while Ginkgo biloba holds immense potential, caution is warranted, as adverse effects such as allergies have been reported, particularly in individuals with known allergies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031047","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":"An Updated Review of Potential Drug Targets for Japanese Encephalitis.","authors":"Roshni Singh, Sayak Sanyal, Nikita Basant, Somali Sanyal","doi":"10.2174/0118715249353956250326164211","DOIUrl":"https://doi.org/10.2174/0118715249353956250326164211","url":null,"abstract":"<p><p>Japanese encephalitis virus (JEV), first identified in 1935, continues to be a major threat to human health, especially in the Asia-Pacific region, where it remains prevalent. JEV, a neurotropic flavivirus, spreads through Culex tritaeniorhynchus mosquito bites and causes severe brain infections with high morbidity and mortality rates. Despite the availability of vaccines, no licensed anti-JEV drugs exist. This review provides a comprehensive overview of the epidemiology, structural and nonstructural proteins, and pathogenesis of JEV and explores potential drug targets. This study highlights both conventional and nonconventional drug targets, with a focus on nonstructural JEV proteins, which may hold promise for therapeutic development. This review also discusses drug targets shared by JEV and other flaviviruses, such as dengue, Zika, and West Nile virus, which reveal common pathways for viral entry and replication, along with distinct mechanisms specific to JEV. Key receptor interactions, including DC-SIGN, TAM receptor, sialic acid, LDLR, and CLEC5A interactions, are involved in JEV transmission and immune evasion. Additionally, the NMDA receptor has been identified as a critical player in JEV pathogenesis, suggesting new opportunities for neuroprotective therapies. A major obstacle in JEV drug development is the blood-brain barrier (BBB), which hinders the delivery of therapeutic agents to the central nervous system (CNS). Recent research has emphasized the need for innovative drug delivery systems that can cross the BBB, reducing viral replication and neural damage. While clinical trials with traditional antivirals have yielded mixed results, live attenuated and inactivated vaccines have shown promise in preventing JEV infection. Additionally, nucleic acid-based therapies, including microRNAs and short hairpin RNAs (shRNAs), are emerging as potential treatments, with nanoparticle-based delivery systems offering solutions to overcome BBB challenges. This review underscores the need for an integrated approach, including improved vaccines, targeted drug delivery strategies, and novel therapeutics, to effectively combat JEV infections on a global scale.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026608","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}