CNS & neurological disorders drug targets最新文献

{"title":"Syntaxin-4 at the Crossroads of Synaptic Plasticity and Neurodegeneration: From Molecular Mechanisms to Biomarker and Therapeutic Potential.","authors":"Yue Li, YunSong Wei, JingBo Zhao, PuSheng Quan, Cheng Wang, Mingfang Jiang","doi":"10.2174/0118715273465885260623094946","DOIUrl":"https://doi.org/10.2174/0118715273465885260623094946","url":null,"abstract":"<p><p>Syntaxin-4 (Stx4), a member of the Qa-SNARE protein family, is a pivotal regulator of membrane trafficking. Stx4 is predominantly localized at the postsynaptic membrane of neurons and in glial cells, where it is essential for synaptic plasticity and the maintenance of neuronal homeostasis. Stx4 facilitates the activity-dependent exocytosis of glutamatergic receptors, thereby governing the balance between Long-Term Potentiation (LTP) and Long-Term Depression (LTD). Emerging evidence suggests that dysregulation of Stx4 is intricately linked to the pathogenesis of neurodegenerative diseases. In Alzheimer's disease, Stx4 is involved in synaptic dysfunction and cognitive impairment through its interactions with amyloid-β (Aβ) and tau pathologies, affecting receptor recruitment at dendritic spines. In Parkinson's Disease (PD), Stx4 contributes to α-synuclein proteostasis, dopaminergic signaling, neuroinflammation, and the maintenance of blood-brain barrier integrity. While its presence in cerebrospinal fluid highlights its potential as a candidate biomarker for these diseases, further validation is required to establish clinical utility. This review summarizes current mechanistic insights into Stx4's multifaceted roles in the neurodegenerative disorders and explores the therapeutic prospects of targeting Stx4-mediated pathways due to its translational potential.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457994","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":"miR-206-mediated Regulation in Depression: From Pathophysiological Mechanisms to Intranasal AntagomiR-206 Therapy.","authors":"Yu-Chi Zhuang, Wei Guan","doi":"10.2174/0118715273480036260623080843","DOIUrl":"https://doi.org/10.2174/0118715273480036260623080843","url":null,"abstract":"<p><p>Depression is a globally prevalent mental disorder characterized by persistent low mood and cognitive deficits, with high incidence and recurrence rates, causing a heavy burden on individual health and public health systems worldwide. MicroRNAs (miRNAs), a class of single-stranded noncoding RNAs (ncRNAs) composed of 18-25 nucleotides, regulate gene expression at the posttranscriptional level by binding to the 3' UTR of target mRNAs. Due to their ability to inhibit translation and their high enrichment in brain tissue, miRNAs have become key players in depression research, with increasing evidence supporting their potential as diagnostic biomarkers and therapeutic targets for the disease. Among these miRNAs, miR-206 is considered a critical regulator of stress susceptibility and is highly expressed in brain regions associated with depression, including the hippocampus and prefrontal cortex (PFC). Numerous preclinical studies have confirmed the role of miR- 206 in stress responses. However, the precise neurobiological mechanisms involved in depression, including its regulation of neurogenesis, neuroinflammation, the gut-brain axis, and interactions with key molecules such as BDNF, remain incompletely understood. This review synthesizes the latest research progress on miR-206, focusing on its multifaceted involvement in the pathophysiology of depression. By summarizing findings on its downstream signaling pathways, tissue-specific expression patterns, and regulatory effects on antidepressant effects such as ketamine-mediated regulation, this study aims to provide new insights into the diagnosis and treatment of major depressive disorder (MDD) and offer important guidance for the development of next-generation antidepressant drugs.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457920","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":"Role of Cholesterol Metabolism in the Link Between Diabetes and Alzheimer's Disease.","authors":"Pratishtha Sharma, Rohinee Dodiya, Dipa K Israni, Devesh U Kapoor","doi":"10.2174/0118715273444881260119053309","DOIUrl":"https://doi.org/10.2174/0118715273444881260119053309","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 Diabetes Mellitus (T2DM) and Alzheimer's Disease (AD) share complex metabolic disturbances, with cholesterol dysregulation emerging as a central mechanistic link. Although brain cholesterol metabolism operates largely independently of peripheral lipid pools, it is highly susceptible to disruption, particularly in the insulin-resistant ApoE4 genotype.</p><p><strong>Methods: </strong>This review follows a structured literature approach using PubMed, Scopus, and Web of Science (2000-2025) to critically evaluate mechanistic and translational evidence on cholesterol- T2DM-AD interplay. It critically evaluates current evidence on cholesterol production, transport, and elimination in the Central Nervous System (CNS), focusing on the roles of astrocytes, neurons, and transporters such as ATP-binding cassette transporter A1 (ABCA1). It also explores how peripheral metabolic stress in T2DM affects central cholesterol homeostasis and contributes to amyloid- beta (Aβ) accumulation and neurodegeneration. Pharmacological approaches targeting cholesterol regulation, including statins, liver X receptor (LXR) modulators, and glucagon-like peptide-1 (GLP-1) receptor agonists, are discussed.</p><p><strong>Results: </strong>Findings indicate that impaired cholesterol regulation disrupts neuron-astrocyte interactions, enhances Aβ deposition, and accelerates neurodegeneration. Controversies remain regarding the relative impact of peripheral vs. central cholesterol imbalance and Blood-Brain Barrier (BBB) permeability in therapy. In T2DM, peripheral insulin resistance and hypercholesterolemia exacerbate central cholesterol imbalance, thereby intensifying AD pathology. Emerging therapeutic studies suggest that modulation of cholesterol pathways may reduce neuroinflammation, promote Aβ clearance, and slow cognitive decline.</p><p><strong>Discussion: </strong>The overlap between T2DM and AD highlights cholesterol metabolism as a pivotal pathogenic axis. While peripheral factors worsen central dysregulation, CNS-specific disturbances independently drive disease progression. Targeted modulation of cholesterol pathways, through statins, LXR modulators, and GLP-1 agonists, shows promise but demands precision approaches tailored to genotype and BBB permeability.</p><p><strong>Conclusion: </strong>The cholesterol-AD-T2DM axis represents a promising therapeutic target. Addressing cholesterol dysregulation could enable novel, personalized strategies to mitigate neurodegeneration and cognitive decline.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280291","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":"Linking Neurodegeneration and Age-related Macular Degeneration: Unified Pathways and Intervention Strategies.","authors":"Shubhangi Mukherjee, Suman Kumar Ray, Sukhes Mukherjee","doi":"10.2174/0118715273450093260523224914","DOIUrl":"https://doi.org/10.2174/0118715273450093260523224914","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is caused by the degeneration of photoreceptors and retinal pigment epithelium (RPE) along with drusen deposition and is the leading cause of vision loss in older adults. Both these structures within the central nervous system (CNS) utilize common neuro-inflammatory mechanisms because the retina is an outgrowth of the brain. Like the brain, the eye has its own physical characteristics and surface molecules as well as a tendency towards specific immune reactions. Numerous distinct neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Frontotemporal dementia (FTD) that impact the brain present as eye symptoms, and the conventional diagnosis of these neurodegenerative disorders (NDs) is often preceded by ocular symptoms. Furthermore, several eye-specific disorders have characteristics in common with other CNS disorders. NDs and AMD share common key features, such as tau and amyloid-β deposits, oxidative stress response, chronic inflammation, and dysregulation of microglia and müller glia. Common pathological mechanisms include complement activation, amyloid aggregation, neuroinflammation, vascular impairment, and cell death, providing a basis for a convergent neuroimmune axis between retinal and cerebral degeneration. Comparing these age-related diseases will facilitate the identification of shared risk factors, convergent molecular pathways, and potential cross-applicable therapeutic strategies, such as anti-inflammatory, anti-complementary, anti-apoptotic, and anti-VEGF-based approaches. This knowledge may enhance understanding of neurodegenerative diseases, help identify early biomarker development for diagnosis, and enable the design of targeted therapeutic strategies.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267341","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":"Modulating the Microbiota-gut-brain Axis: A Promising Strategy for Alzheimer's Disease Prevention and Management.","authors":"Ritu Kainth, Ajay Singh Kushwah","doi":"10.2174/0118715273444471260608194550","DOIUrl":"https://doi.org/10.2174/0118715273444471260608194550","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder evident by cognitive decline and neuropathological hallmarks such as amyloid-β (Aβ) plaques and tau protein hyperphosphorylation. Recent evidence links gut microbiota dysbiosis to AD pathogenesis through the microbiota-gut-brain axis (MGBA), a complex bidirectional communication system entailing neural, immune, and metabolic pathways. This study aims to explore the mechanistic relationship between gut microbiota alterations and AD development and to assess the therapeutic potential of microbiota modulation through dietary, probiotic, and metabolite-based interventions. A thorough analysis was undertaken, blending evidence from preclinical animal models and clinical investigations. The effects of bacterial metabolites, microbial components (e.g., lipopolysaccharides, microbial amyloids), and interventions like probiotics, dietary fibers, and polyphenols were examined. Emphasis was placed on neuroinflammatory markers, Aβ deposition, blood-brain barrier integrity, and behavioral outcomes. Findings revealed that gut dysbiosis contributes to increased neuroinflammation, microglial activation, reduced short-chain fatty acid (SCFA) levels (especially butyrate), and compromised blood-brain barrier function. Bacterial LPS and amyloids may enhance Aβ aggregation and tau hyperphosphorylation. Probiotic supplementation and high-fiber/polyphenol-rich diets were noticed to restore microbial balance, increase SCFA production, attenuate Aβ deposition, and improve cognitive functions in animal models. Modulating gut microbiota shows potential as a complementary strategy for delaying or managing AD. Restoration of microbial equilibrium via dietary or probiotic approaches can mitigate neurodegeneration by targeting inflammation, microbial metabolite production, and immune responses. Further mechanistic studies and longitudinal human trials are needed to validate the clinical efficacy of MGBA-targeted therapies. Personalized microbiome-based interventions may pave the way for novel, non-invasive strategies to combat AD progression.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267386","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 Therapeutic Effects of Dietary Supplements on OCD: A Narrative Review.","authors":"Ghazal Tavakoli, Leili Sharif Bakhtiar, Amir Ghanbari, Poorya Mohammadzadeh, Mahya Ghodousi, Kiana Kimiaei Asadi, Farzad Sheikhzadeh, Roshanak Amirian, Farhad Nikzad, Ehsan Ghoushi, Sepehr Olangian-Tehrani, Mohadeseh Poudineh","doi":"10.2174/0118715273429122260523223942","DOIUrl":"https://doi.org/10.2174/0118715273429122260523223942","url":null,"abstract":"<p><strong>Introduction: </strong>Sufficient amounts of nutrients have been considered important in the pathophysiology of obsessive-compulsive disorder (OCD). In recent years, many studies have examined alleviating symptoms of neurological and behavioral disorders through nutritional change. Thus, we aim to synthesize current knowledge on serum levels of nutrients and other nutraceuticals and their potential impact on OCD symptoms.</p><p><strong>Methods: </strong>We conducted a targeted literature search of PubMed, EMBASE, and Scopus, including clinical investigations and relevant animal research in June 2025, without applying any publication date restrictions. Articles were selected based on their focus on nutrient interventions and reported OCD-related outcomes.</p><p><strong>Results: </strong>We reviewed evidence on nutritional and neurochemical factors in OCD, including vitamins (B₆, B₉, B₁₂, C, D, and E), mineral supplements (zinc, magnesium, selenium, iron, calcium), glycine, homocysteine, glutamate, N-acetylcysteine, D-cycloserine, omega-3, and inositol, alongside selected pharmacologic neuromodulators including gabapentin, serotonin-targeting agents.</p><p><strong>Discussion: </strong>Notable and relatively consistent differences in homocysteine, glutamate, vitamin B₁₂, and vitamin E, as well as zinc levels, were observed between individuals with OCD and healthy controls, suggesting their potential as biomarkers and therapeutic targets. Preliminary evidence also indicates that supplementation with vitamin C, B₆, B₉, B₁₂, vitamin E, zinc, and N-acetylcysteine may contribute to symptom improvement in OCD.</p><p><strong>Conclusion: </strong>Certain nutritional interventions appear to offer safe, well-tolerated adjunctive benefits in OCD treatment, likely through anti-inflammatory and antioxidant pathways. However, because of heterogeneity in study designs, small sample sizes, and variable dosing regimens, further research should determine optimal supplement types, dosages, and treatment durations.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267349","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":"Mitochondrial Dysfunction in Parkinson's Disease: Diagnostic and Therapeutic Advances.","authors":"Gang Wu, Xiao-Lin Dong, Rui Li, Fu-Rong Jin, Jing-Ting Lu, Lian-Bing Lin","doi":"10.2174/0118715273454275260601070029","DOIUrl":"https://doi.org/10.2174/0118715273454275260601070029","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is a neurodegenerative disorder in which mitochondrial dysfunction plays a central role in pathogenesis. This review summarizes key mitochondrial abnormalities involved in PD, including respiratory chain impairment, dysregulation of mitochondrial dynamics, defective mitophagy, and mitochondrial DNA (mtDNA) damage. It further examines how these processes interact with α-synuclein (α-syn) pathology, contributing to increased vulnerability of dopaminergic neurons. In addition, current diagnostic approaches are transitioning from isolated biomarkers to an integrated Mitochondrial Health Index (MHI) for improved early detection. Finally, a critical appraisal of therapeutic interventions is presented, emphasizing the shift from monotherapies to multifaceted combination strategies. This review delineates a strategy for transformative PD therapies.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207253","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":"Understanding the OMA1-DELE1-HRI Axis and PINK1-parkin-mediated Mitophagy in Parkinson's Disease.","authors":"Shalini Singh, Anisha Sharma, Ravi Kumar Rajan, Manodeep Chakraborty, Ananya Bhattacharjee","doi":"10.2174/0118715273469080260515103009","DOIUrl":"https://doi.org/10.2174/0118715273469080260515103009","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial dysfunction plays a crucial role in the pathogenesis of Parkinson's disease (PD). PINK1-Parkin-mediated mitophagy is a quality-control system for mitochondria that protects neurons by getting rid of damaged mitochondria. The OMA1-DELE1-HRI axis has recently been recognized as a vital regulatory checkpoint that limits excessive mitophagy and prevents metabolic failure during mitochondrial stress. The aim of this review is to analyze the mechanistic interplay between the PINK1-Parkin pathway and the OMA1-DELE1-HRI signaling axis. This study aims to synthesize current research on the influence of the stress-response pathway on the initiation of mitophagy, maintenance of mitochondrial homeostasis, and neuronal survival in PD.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted of molecular, genetic, and pharmacological studies on OMA1, DELE1, and HRI. A thorough analysis of data from kinome-wide screening assays, genetic knockdown experiments, multi-omics profiling, and structural biology studies was performed to elucidate the regulatory interactions between HRI and PINK1 under mitochondrial stress conditions.</p><p><strong>Result: </strong>The OMA1-DELE1-HRI pathway stops PINK1 from being stable by controlling how mitochondria make proteins and how they respond to stress. This inhibition serves as a metabolic safeguard that regulates mitophagy levels, preventing harmful overactivation. HRI seems to change PINK1-dependent mitophagy while having little effect on other pathways that clear things at the same time. This suggests that HRI has different substrate preferences and signaling specificity.</p><p><strong>Discussion: </strong>The OMA1-DELE1-HRI axis is an important negative regulator of mitophagy that PINK1 and Parkin mediate. It stops too much mitochondrial clearance and metabolic failure in Parkinson's disease. This mechanism preserves bioenergetic homeostasis and promotes neuronal survival, suggesting that HRI is a promising therapeutic target. Inhibitors like ISRIB or heme mimetics may selectively restore mitophagy, thereby enhancing neuroprotection and enabling precision therapies guided by biomarkers such as phosphorylated eIF2.</p><p><strong>Conclusion: </strong>The OMA1-DELE1-HRI axis is a distinctive regulatory mechanism for mitochondrial quality control, significantly impacting neuroprotection in Parkinson's disease. Understanding its dual role in controlling mitophagy and maintaining bioenergetic homeostasis opens new possibilities for targeted drug development. Subsequent research should focus on structural and pharmacological modifications of HRI to enhance mitophagy while preventing mitochondrial depletion.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207197","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":"KCNQ2 Channel as a Druggable Epilepsy Target: Advances in Pharmacological Modifiers.","authors":"Inn-Chi Lee, Shi-Bing Yang, Swee-Hee Wong, Jiann-Jou Yang, Shuan-Yow Li","doi":"10.2174/0118715273455571260523060433","DOIUrl":"https://doi.org/10.2174/0118715273455571260523060433","url":null,"abstract":"<p><p>KCNQ2 encodes the Kv7.2 channel, which mediates the M-current and regulates neuronal excitability. Pathogenic variants of KCNQ2 are associated with a spectrum of neonatal epilepsies, ranging from self-limited familial neonatal epilepsy to severe Developmental and Epileptic Encephalopathy (DEE), characterized by early seizure onset within the first week after birth, seizure clustering, and poor long-term neurodevelopment. Despite advances in molecular diagnosis, current treatment options remain limited and are not specific to Kv7.2 modulation, underscoring the need for therapies that target the underlying KCNQ2 channel dysfunction. Pharmacological modifiers of Kv7- mediated currents, such as retigabine, have demonstrated the restoration of impaired M-currents, but safety concerns limit their clinical application. Recent progress has led to the development of nextgeneration Kv7 activators, such as XEN1101, as well as other investigational compounds with improved potency, selectivity, and tolerability. These agents have shown promise for the treatment of epilepsy in adults in both preclinical and clinical studies, but evidence in children remains limited. Indirect modulators acting through sodium channels, GABAergic pathways, or network-level mechanisms may provide seizure control but are less likely to address the underlying channel dysfunction or improve neurodevelopmental outcomes. Challenges persist in translating in vitro efficacy into treatable clinical outcomes, particularly in neonates with DEE. Safety considerations, biomarkers of treatment responsiveness, and neurodevelopmental effects require careful evaluation. Nonetheless, the evolving pharmacological landscape highlights KCNQ2 channels as attractive and druggable targets in epilepsy, offering opportunities for mechanism-based therapies that could transform the management of this rare but devastating DEE.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140261","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":"Lung-Brain Axis Mechanisms of Cognitive Dysfunction in Long COVID.","authors":"Fan Yang, Zhangfan Zhu, Yongqing Wang, Yu Qin, Hongmei Yue","doi":"10.2174/0118715273421593251202095722","DOIUrl":"https://doi.org/10.2174/0118715273421593251202095722","url":null,"abstract":"<p><p>Cognitive dysfunction, characterized by memory impairment, attentional deficits, and executive dysfunction, represents a critical clinical manifestation in post-acute sequelae of COVID-19 that significantly compromises patients' quality of life. The lung-brain axis, as a bidirectional regulatory network connecting the respiratory system to the central nervous system, interacts through neural circuits, humoral pathways, and microbial pathways, and may play a central role in the cognitive impairments occurring in long COVID (LC). This paper systematically reviews the multidimensional pathways of the lung-brain axis and their pathological mechanisms in the cognitive impairment of LC, including direct viral neuroinvasion during the acute phase, chronic injury triggered by viral persistence, immune homeostasis dysregulation, hypoxaemia, microbiome disruption, and renin- angiotensin system imbalance. It then explores clinical intervention strategies based on the lungbrain axis, integrating supportive treatments, such as oxygen therapy, exercise therapy, and cognitive training, with treatments targeting the lung-brain axis, including antiviral drugs, immunomodulation, probiotics, and neuromodulation techniques. It is also suggested that future research should favour the integration of multi-omics technologies and the development of individualised therapeutic targets.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145696","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}