Central nervous system agents in medicinal chemistry最新文献

{"title":"Biomarkers, Diagnostics, and Emerging Therapies in Alzheimer's Disease: A Comprehensive Systematic Review (2015-2025).","authors":"Sunita Patnaik, Pratap Kumar Patra, Chinam Niranjan Patra, Krishna Chandra Panda","doi":"10.2174/0118715249427154260531181405","DOIUrl":"https://doi.org/10.2174/0118715249427154260531181405","url":null,"abstract":"<p><strong>Introduction: </strong>The underlying association between multiple risk factors like age, preexisting diseases, infections, traumatic brain injuries, and certain genetic factors makes the diagnosis and treatment a challenge in AD. Identification of biomarkers and proper diagnosis of AD could make its management easier. Advances in diagnostic techniques like Positron Emission Tomography (PET) imaging have greatly improved the ability to identify, detect early, monitor disease progression, and manage its therapy.</p><p><strong>Methods: </strong>The recent therapeutic advancements in treatments encompass immunotherapies aimed at amyloid-beta (Aβ) and tau proteins, novel drug delivery systems, non-pharmacological methodologies, and personalised medicine techniques, combination therapies, and non-invasive brain stimulation are important in the management of AD. Cholinesterase inhibitors, such as galantamine, rivastigmine, and donepezil, are used to enhance cognitive performance and reduce confusion. Moderate to severe AD, memantine, a N-methyl-D-aspartate receptor (NMDA) receptor antagonist, is prescribed. Researchers are looking into both active and passive vaccines to get antibodies to Aβ plaques, and monoclonal antibodies, such as Lecanemab and Donanemab, which are used to treat early-stage AD.</p><p><strong>Results: </strong>Ongoing research is focused on identifying new biomarkers and therapeutic targets, advancing gene therapy, and refining immunotherapeutic approaches for AD.</p><p><strong>Discussion: </strong>There is growing interest in comprehending the influence of lifestyle and environmental factors on the mitigation of AD risk. Ongoing research is essential to elucidate the complexity of AD pathophysiology and to create effective therapies.</p><p><strong>Conclusion: </strong>This review highlights the critical need for future AD research to bridge identified gaps in early detection, focus on improving early diagnosis, developing more effective treatments, refining existing drugs and therapies, and understanding the underlying disease progression mechanisms.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809561","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":"Multi-Target Neuroprotection by Phytochemicals: Mechanisms, Clinical Evidence, and Translational Strategies for Neurodegenerative Disorders.","authors":"Banaja Panigrahi, Ashutosh Nayak, Satyabrata Nanda, Ashirbad Nanda, Biswa Mohan Sahoo","doi":"10.2174/0118715249477103260720063338","DOIUrl":"https://doi.org/10.2174/0118715249477103260720063338","url":null,"abstract":"<p><strong>Introduction: </strong>Neurological disorders (NDs) represent a significant and rapidly increasing global health problem, resulting in the progressive loss of neurons and cognitive decline. Current treatments are symptomatic and have major side effects. This review provides a detailed discussion on the roles and modes of action of the phytocompounds, their mechanistic pathways, and the challenges and opportunities, along with their clinical translation.</p><p><strong>Method: </strong>Relevant literature published in peer-reviewed journals was collected from databases including PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using keywords related to phytochemicals, neuroprotection, oxidative stress, inflammation, and neurological disorders. Studies focusing on the mechanistic and therapeutic roles of plant-derived bioactive compounds were critically analyzed.</p><p><strong>Results: </strong>The application of different phytocompounds, including polyphenols, flavonoids, alkaloids, and terpenoids, is discussed. In addition, the roles and modes of action of phytocompounds such as curcumin, resveratrol, and epigallocatechin gallate (EGCG) have been discussed in relation to oxidative stress, inflammation, and protein aggregation. Their therapeutic actions are mediated via key mechanistic pathways, such as NF-κB inhibition, Nrf2/ARE activation, anti- apoptotic effects, neurotransmitter regulation, and chelation of redox-active metals.</p><p><strong>Discussion: </strong>Emerging evidence suggests that phytochemicals may mitigate oxidative stress, neuroinflammation, and neuronal damage associated with NDs. However, variability in phytochemical composition and insufficient clinical validation remain major concerns. Phytochemicals possess multi-target neuroprotective activities and may serve as promising therapeutic candidates for NDs. Challenges and Future Directions: The existing limitations, such as poor bioavailability, lack of standardization, and regulatory barriers, prevent clinical translation. The recent advances, including nanocarrier-based delivery of plant-derived drugs, artificial intelligence-driven phytocompound modelling, and pharmacogenomics-based personalized therapy, have been discussed.</p><p><strong>Conclusion: </strong>Phytochemicals hold significant promise for neurotherapeutics. Nevertheless, their clinical application in several NDs requires advances in targeted drug delivery systems, precision medicine, standardized formulations, and robust mechanistic and clinical studies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708928","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 Comprehensive Review on Compounds and Herbal Approaches against Amyloid Beta Aggregation in Alzheimer's Disease.","authors":"Zulfa Nooreen","doi":"10.2174/0118715249416202251209125536","DOIUrl":"https://doi.org/10.2174/0118715249416202251209125536","url":null,"abstract":"<p><p>Alzheimer's disease is a neurodegenerative disorder that affects brain cells over time, progressively reducing cognitive function, interfering with memory retention, and making daily tasks more difficult. The development of amyloid-beta (Aβ) plaques plays an important role in the progression of the disease, contributing to neurological swelling and cognitive impairment. Aβ induces oxidative damage and produces anti-inflammatory cytokines while reducing the association with vascular RAGE and acetylcholine. This article aims to present the latest and relevant research on treatment approaches targeting amyloid beta, including synthetic compounds, phytomolecules, and plant extracts. Novel delivery approaches are also covered. Memantine, latrepirdine, somatostatin, diosgenin, cirsiliol, amentoflavone, luteoloside, and many other synthetic compounds have been reported to generally inhibit Aβ aggregation, thereby reducing plaque development. Phytomolecules such as brazilin, (+)-catechin, ginnalin A, bacoside-A, bakuchiol, curcumin, homotaurine, icariin, genistein, fucosterol, and quercitrin also alleviate symptoms via various mechanisms. Additionally, plant extracts from Annona atemoya, Lycium barbarum, Humulus lupulus, Oroxylum indicum, Salvia macilenta, Trichosanthis Semen, Camellia sinensis, Betula utilis, Cirsium japonicum, Elaeagnus glabra, Orthosiphon aristatus, Metasequoia glyptostroboides, Zizania latifolia, and Benincasa hispida are discussed briefly with their mechanisms of action. The present review also addresses the pathogenesis, risk factors, symptoms, and diagnosis of amyloid beta aggregation. Data were collected from PubMed, ScienceDirect, SciFinder, Scopus, and Google Scholar.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457996","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":"Stimuli-responsive Lipid-based Nanoplatforms for Targeted Therapy of Brain Diseases: Current Challenges and Future Directions.","authors":"Vaishnavi Chavan, Shweta Jadhav, Fatima Jatrate, Gayatri Jondhalkar, Chandraprabhu Jangme, Prachi Mhettar","doi":"10.2174/0118715249462564260518110221","DOIUrl":"10.2174/0118715249462564260518110221","url":null,"abstract":"<p><p>The reported research revealed the peculiarity of stimuli-responsive lipidic nanocarriers for localised therapy in distinct brain diseases, as it is supremely challenging due to the complexity of the brain. The pitfalls of conventional carriers could be carefully addressed utilising these smart lipidic nanoparticles due to their versatile features. The meticulous depiction of cardinal strategies for boosting barrier penetration with a mechanism paves the roadmap for lipidic nanoparticles in targeting. The present review article offers viewpoints on the application of distinct endogenous stimuli, like pH, hypoxia, and enzymes, along with exogenous stimuli, such as temperature, magnetism, and light. Each stimulus elaborated their exploitation of pathophysiological changes during diseased conditions, and its mechanism of utilisation in treating the diseases protects healthy cells from damage. Importantly, the detailed emphasis on the role of lipidic nanocarriers and their key advantages, including biosafety, biocompatibility, and high payload, offers a new avenue for targeted therapies. The stimuli-responsive lipid-nanoparticle-mediated targeted therapy in conditions like neurodegenerative diseases (Alzheimer's and Parkinson's), tumours like glioblastoma multiforme (GBM), infectious conditions like meningitis, and traumatic conditions like intracerebral haemorrhage are discussed in this work. Despite advancements, fewer issues like nanotoxicity, controlled size, scalability, and distribution within the brain appear to have more solutions. In future multi-stimuli applications, biomolecule integration and clinical translation could resolve many of the drawbacks of the present situation. Concisely, in the future, stimuli-responsive lipid nanoparticles will serve as an intriguing approach for targeted therapy in brain diseases.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431662","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":"Phyto-Nanotherapeutics for Alzheimer's Disease: Current Progress and Future Perspectives.","authors":"Anushka Sharma, Awaneet Kaur, Javed Khan, Himani Pandey","doi":"10.2174/0118715249455878260609100548","DOIUrl":"https://doi.org/10.2174/0118715249455878260609100548","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive and behavioral impairment and represents a major cause of dementia worldwide. It primarily affects the elderly population. The disease is marked by progressive neuronal damage, leading to impairments in cognition, behavior, emotions, and communication. Although currently available therapies provide symptomatic relief, they fail to alter disease progression, necessitating the development of more effective therapeutic strategies. Phytoconstituents have gained considerable attention due to their neuroprotective properties and multitargeted mechanisms of action against pathways implicated in AD. However, their clinical application is limited by poor Blood-Brain Barrier (BBB) permeability, low bioavailability, and inadequate solubility. Nanotechnology offers a promising approach for brain-targeted drug delivery by enhancing the therapeutic efficacy of phytoconstituents through advanced nanocarrier systems. This review explores the synergistic potential of phytoconstituents and nanocarriers for the management of AD, aiming to improve therapeutic outcomes and overcome existing limitations. It further highlights the integration of medicinal plant-based compounds with nanotechnology as a novel strategy for AD treatment. The combination of nanocarriers and phytoconstituents may facilitate enhanced BBB penetration and improved neuroprotection. Notably, nanomedicine- based approaches, including phytoconstituent-loaded nanoparticles and liposomes, demonstrate significant potential to overcome delivery barriers and enable efficient drug transport to the brain.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148399914","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":"Cannabinoids for Neuropathic Pain: A Pharmacological Review of Mechanisms, Clinical Translation, and Future Directions.","authors":"Shrishti Tyagi, Shreya Shrivastava, Vipin Kumar, Satyender Kumar, Sachin Gulia, Ujjawal Singh, Megha Thakur","doi":"10.2174/0118715249440429260616140926","DOIUrl":"https://doi.org/10.2174/0118715249440429260616140926","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Neuropathic pain (NP) continues to be a significant clinical issue because the existing treatment modalities have very low efficacy and tolerability. An increasing body of mechanistic and translational data is identifying the endocannabinoid system (ECS) as a key regulator of nociceptive transmission, neuroinflammation, and maladaptive synaptic plasticity. This review critically synthesizes preclinical actions, pharmacological variety, and clinical trial evidence supporting cannabinoid-based interventions to NP, alongside identifying translational challenges, safety concerns, and emerging precision- medicine strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The approach adopted was a narrative review approach. To identify the relevant literature, published within the last two decades, PubMed, Scopus, Web of Science, Google Scholar were searched using the keywords that are related to cannabinoids, endocannabinoid system, neuropathic pain, phytocannabinoids, and clinical trials. Relevance was used to select preclinical, mechanistic, and clinical studies. The article is written in the form of a narrative review and is not organized in the system of a systematic review.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The preclinical evidence demonstrates that cannabinoids regulate NP by acting through CB1- and CB2-mediated, inhibitory effects on the release of neurotransmitters, central sensitization, neuroinflammation and regulation of transient receptor potential (TRP) channels. Phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as synthetic cannabinoids, are effective in various experimental NP models. Clinical trials report variable but clinically significant decreases in the intensity of pain, sleep disturbance, and allodynia; although results vary depending on formulation, dose, route of administration, and heterogeneity of patients. Safety data show dose-related adverse effects, such as dizziness, cognitive impairment, and psychoactive effects, with CBD showing a relatively positive tolerability profile. Although there is a high level of mechanistic support, the translation to consistent clinical benefit is still limited due to pharmacokinetic variability, variation in the ratio of THC:CBD, and patient-specific factors. Other issues are standardization of formulations, safety testing in the long term, and variability in regulations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The varied actions of cannabinoids on NP pathophysiology, through CB1/CB2 agonism, neuroinflammation suppression, and TRP modulation, are strongly supported by preclinical evidence, but are hampered by pharmacokinetic variability, inconsistent THC: CBD ratios and inconsistent patient response. CBD has a good tolerability despite the challenges such as regulatory barriers and lack of long-term safety evidence, which highlights the potential of CBD in precision tactics. To enhance the reliability of treatments, our findings demonstrate that th","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148398829","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":"Bioinformatic Identification of Shared Gene Networks Between Weaning- Induced Intestinal Inflammation and Neuroinflammatory-Related Pathways.","authors":"Oumaima Anachad, Wafaa Taha, Chaimaa Saadoune, Adbelkarim Ezaouine, Badreddine Nouadi, Faiza Bennis, Fatima Chegdani","doi":"10.2174/0118715249457554260605114916","DOIUrl":"https://doi.org/10.2174/0118715249457554260605114916","url":null,"abstract":"<p><strong>Introduction: </strong>Weaning is a critical developmental stage that can trigger intestinal inflammation through disruption of microbial homeostasis, immune responses, and epithelial barrier integrity. While numerous studies have explored gene expression changes during weaning in animals, no comparable analyses have been conducted in humans. Given the close physiological and genetic similarity between pigs and humans, piglet data were employed to investigate the molecular mechanisms underlying weaning-induced intestinal inflammation and its potential links to neurological pathways.</p><p><strong>Methods: </strong>A curated set of 117 differentially expressed genes related to gut inflammation was collected from bibliographic sources. Protein-protein interaction network analysis was performed using NetworkAnalyst and Cytoscape, followed by hub gene selection and functional enrichment using KOBAS, ClusterProfiler, and StringApp.</p><p><strong>Results: </strong>Among the identified hub genes, SOD1, CAT, TNF, CXCR4, TLR2, and TGFB1 play key roles in oxidative stress, immune response, glial regulation, and neuroinflammatory signaling. Enrichment analysis revealed significant associations with pathways such as Amyotrophic Lateral Sclerosis, TGF-β signaling, Folate and Vitamin B12 metabolism, and Inflammatory Bowel Disease, as well as biological processes like gliogenesis, hypoxia response, and cytokine signaling.</p><p><strong>Discussion: </strong>These findings suggest that intestinal inflammation during weaning may have systemic implications, highlighting shared molecular pathways relevant to neuroinflammatory-related processes.</p><p><strong>Conclusion: </strong>This study provides new insight into the genetic and molecular landscape of weaning-induced inflammation and its broader systemic effects. The identified shared molecular pathways may provide a foundation for future experimental studies investigating the broader biological implications of early-life intestinal inflammation.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378639","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":"Heterocyclic Scaffolds as Therapeutic Agents in Multiple Sclerosis: Mechanisms and SAR Study.","authors":"Ashish Yadav, Niranjan Kaushik, Deepika Paliwal, Aman Thakur, Abhishek Maurya, Rakesh Sahu","doi":"10.2174/0118715249500184260615144738","DOIUrl":"https://doi.org/10.2174/0118715249500184260615144738","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a progressive, immune-mediated condition characterized by the destruction of myelin, the protective insulation surrounding nerve fibers. This ongoing assault triggers a cascade of damage, including persistent inflammatory responses, loss of myelinproducing oligodendrocytes, axonal degradation, and cumulative neurological impairment. While motor and sensory difficulties are hallmark features, patients frequently contend with less visible but equally debilitating symptoms such as cognitive dysfunction, profound fatigue, affective disorders, nerve pain, and autonomic instability. These often-overlooked manifestations critically impact well-being and functional capacity. The pathophysiology of MS is increasingly understood as a network of overlapping cellular and molecular dysfunctions. Alongside irregularities in the endocannabinoid signaling network, key contributors include aberrant immune communication, persistently activated microglia, impaired mitochondrial energy production, and dysregulated activity of enzymes like PDE7, MAGL, ROCK, and PADs. These interconnected pathways collectively drive disease initiation and advancement. This analysis synthesizes established information on current FDA-approved treatments for MS and examines promising novel small-molecule compounds aimed at specific disease-relevant targets. A significant focus is placed on medicinal chemistry advancements, particularly the design and optimization of heterocyclic compounds. Scaffolds incorporating quinolines, pyrimidines, indoles, and related nitrogen-containing structures demonstrate considerable potential for conferring immunomodulation, reducing inflammation, and protecting neural tissue. By evaluating structure-activity relationships, binding mechanisms, and strategic drug design, this review offers an integrated perspective to inform the creation of new, targeted therapies for MS.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378568","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":"Fluorinated Gamma-carboline Derivatives as Promising Neuroprotective Candidates. Structure-Activity Relationships.","authors":"Maria A Lapshina, Elena F Shevtsova, German L Perlovich, Alexey A Ustyugov, Alexey Y Aksinenko, Daria V Vinogradova, Vladimir P Fisenko, Tatyana V Volkova, Olga R Simonova, Maria N Zakharova, Sergey O Bachurin","doi":"10.2174/0118715249452954260531175501","DOIUrl":"https://doi.org/10.2174/0118715249452954260531175501","url":null,"abstract":"<p><strong>Introduction: </strong>The structure-property relationship of drug candidates determines their transport to target organs and is used as a tool to design drugs with optimal properties and minimal undesirable effects. The effects of fluorinated derivatives of gamma-carboline on the formation of cytosolic aggregates of the FUS protein and the relationships among structure, physicochemical characteristics, and anti-aggregation properties were studied.</p><p><strong>Methods: </strong>The effect of the compounds on FUS protein aggregation in SH-SY5Y cells was evaluated using confocal fluorescence microscopy. Partition coefficients were determined using the isothermal saturation method, and all descriptors were calculated with a software package.</p><p><strong>Results: </strong>A series of fluorinated γ‑carboline derivatives was synthesized and demonstrated the ability to reduce pathological FUS protein aggregation in a cellular model of proteinopathy. The influence of substituents on the distribution coefficients of the studied compounds was revealed. Among the most active compounds, this study highlights DF-302 and DF-402, which feature a methyl group and a trifluoromethyl group on the pyridinium fragment, respectively.</p><p><strong>Discussion: </strong>The structure-activity relationships for the inhibition of FUS protein aggregation by fluorinated γ-carbolines were analyzed in relation to their physicochemical properties. A linear correlation was observed between the anti-aggregation efficacy and the total hydrogen bond acceptor capacity: as the compound's propensity to form hydrogen bonds with the FUS protein increased, its ability to prevent large aggregate formation in cells decreased. An assumption has been made that off-target interactions of the studied compounds with membrane proteins increase with their hydrogen bond acceptor capacity. This effect can limit compounds' availability to influence the processes of cytosolic FUS protein aggregates.</p><p><strong>Conclusion: </strong>The positive correlation of lipophilicity with FUS aggregate reduction underscores the role of cellular penetration in the anti-aggregation effect. Conversely, the negative correlation with hydrogen-bond acceptor capacity suggests that off-target interactions with membrane proteins may compete with binding to FUS aggregates.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347721","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":"D-galactose-induced Cognitive Impairment: Mechanism, Models and Therapeutic Interventions.","authors":"Tanisha Chaudhary, Sagarika Majhi, Meenakshi Sharma","doi":"10.2174/0118715249462013260509045906","DOIUrl":"https://doi.org/10.2174/0118715249462013260509045906","url":null,"abstract":"<p><p>Age is the main risk factor for cognitive impairment, a degenerative disorder marked by deficiencies in memory, learning, and executive function. Although natural ageing research necessitates longer timeframes, animal models are crucial for comprehending causes and creating therapies. Rapid mechanistic study and treatment screening are made possible by the D-galactoseinduced ageing model, induces age-like cognitive and metabolic characteristics in few weeks. A comprehensive literature search was conducted using major scientific databases, including ScienceDirect and Google Scholar. The D-galactose model's current understanding is summarised in this thorough study, which also covers therapeutic approaches, comparative comparison with other ageing models, and molecular pathways. Exposure to D-galactose sets off a series of pathogenic processes that culminate in neuronal malfunction and cognitive impairment. These processes include oxidative stress, advanced glycation end-product (AGE) production, NF-κB and MAPKmediated inflammation, endoplasmic reticulum stress, and apoptosis. With the benefits of quick induction and repeatable outcomes, the model replicates many characteristics of normal ageing, such as cognitive impairments, oxidative damage, and neuroinflammation. Antioxidants (taurine, thymoquinone), anti-inflammatory substances (shikonin, osthole), anti-glycation products, ER stress modulators, and multi-target therapies are among the many therapeutic approaches that have shown promise in the D-galactose model. The model is useful for quick screening and mechanistic hypothesis testing, but further models and clinical research are needed for translational validation.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145699","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}