CNS & neurological disorders drug targets最新文献

{"title":"The Role of the cGAS-STING Pathway in Central Nervous System Diseases.","authors":"Xiangning He, Xunlu Yin, Qian Chen, Haoyuan Gao, Fangfang Zhao, GuoJun Wang","doi":"10.2174/0118715273428657260309045542","DOIUrl":"https://doi.org/10.2174/0118715273428657260309045542","url":null,"abstract":"<p><p>In recent years, the cGAS-STING signaling pathway has emerged as a highly regarded mechanism for intracellular DNA recognition and innate immune activation. This pathway activates downstream interferon and inflammatory factor expression by recognizing Double-Stranded DNA (dsDNA) in the cytoplasm, thereby participating in the regulation of various physiological and pathological processes, including autophagy, apoptosis, and aging. In Central Nervous System (CNS) diseases, abnormal activation of the cGAS-STING pathway is closely associated with key pathological mechanisms such as neuroinflammation and neuronal injury. However, its specific mechanisms of action and regulatory networks in different diseases still require systematic investigation. This paper provides a systematic review summarizing the molecular activation mechanisms of the cGAS-STING signaling pathway, with a focus on elucidating its role and mechanisms of action in various central nervous system disorders. We further explored the potential and challenges of this pathway as a therapeutic target. This paper provides a comprehensive and categorized analysis of the composition, activation process, and functional roles of the cGAS-STING pathway in CNS diseases, based on the latest research findings. By reviewing preclinical research evidence, this study focuses on investigating the activation triggers of this pathway across various disease models and their impact on disease progression. While summarizing current pharmacological research advances targeting this pathway. Reviews indicate that the cGAS-STING pathway is activated in various CNS disorders, primarily exacerbating secondary neurological damage by inducing glial cells to polarize toward a proinflammatory phenotype and perpetuating neuroinflammation. Preclinical studies indicate that cGAS or STING inhibitors (such as C-176, H-151, RU.521, etc.) effectively reduce neuroinflammation and improve behavioral outcomes, suggesting significant therapeutic potential. However, the translational application of this pathway still faces significant challenges, including poor blood-brain barrier penetration of existing inhibitors, suboptimal pharmacokinetic properties, potential off-target toxicity, and the risk of immunosuppression that may arise from long-term inhibition. Moreover, this pathway may exert dual or even opposing effects across different disease stages and cell types, exhibiting significant context-dependent functionality. The cGAS-STING pathway plays a crucial role in neuroimmunoregulation of CNS diseases and represents a highly promising therapeutic intervention target. Despite the exciting preclinical evidence, its translation into clinical applications remains constrained by numerous challenges, including drug delivery, selectivity, safety, and potential interference with physiological immune function. Future research should focus on elucidating the precise regulatory network of this pathway in specific pathological co","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596867","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":"Neuroinflammation, Autophagy, and Neurodegeneration: Mechanisms and Therapeutic Insights.","authors":"Pukar Khanal, Abhishek Balmik","doi":"10.2174/0118715273440234260304000039","DOIUrl":"https://doi.org/10.2174/0118715273440234260304000039","url":null,"abstract":"<p><p>Neuroinflammation and autophagy dysregulation are critical in the pathogenesis of neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's disease. Neuroinflammation occurs after a sustained immune response, which transitions into a chronic pathological state, leading to the sustained generation of pro-inflammatory cytokines and oxidative stress, causing neuronal damage. Meanwhile, defective autophagy exacerbates disease by promoting protein accumulation, e.g., amyloid-β, tau, and α-synuclein, thereby enhancing neuroinflammation. In this review, we focus on critical pathways, including mTOR and AMPK, that regulate these events and illustrate how their dysregulation may lead to a vicious cycle of inflammation and autophagy dysfunction. Novel therapeutic strategies, including mTOR inhibitors, autophagy enhancers, and inflammasome modulators, may contribute to cellular homeostasis. Furthermore, approaches that promote upregulation of chaperone- mediated autophagy can enable selective clearance of mediators of inflammatory response and aggregated/misfolded proteins. Advanced approaches such as CRISPR-based gene editing and RNA therapeutics provide tools to target molecular mechanisms involved in these neurodegenerative disorders, whereas the development of reliable biomarkers and novel delivery strategies may pave the way for personalized treatments. Moreover, artificial intelligence-based workflows and models may strengthen phenotypic and mechanistic screening of autophagy modulators and potential drug targets. By incorporating these forthcoming insights, this review underscores the critical need for comprehensive therapies that target both neuroinflammation and autophagy dysfunction to mitigate disease progression and improve patient outcomes.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596819","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":"NEAT1 as a Diagnostic Biomarker and Therapeutic Target for Alzheimer's Disease: A Comprehensive Review.","authors":"Mohammad Yasin Zamanian, Olga F Belaia, Zhanna R Gardanova","doi":"10.2174/0118715273431267260210124040","DOIUrl":"10.2174/0118715273431267260210124040","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is marked by progressive cognitive decline and memory loss. Emerging evidence underscores the role of long non-coding RNAs (lncRNAs), particularly nuclearenriched abundant transcript 1 (NEAT1), in AD pathogenesis. NEAT1, a pivotal lncRNA that regulates diverse cellular processes, shows dysregulated expression in AD and impairs neuronal survival. This review explores NEAT1's molecular mechanisms, biomarker potential, and therapeutic relevance. NEAT1 contributes to AD pathology by acting as a competitive endogenous RNA (ceRNA) that sequesters protective microRNAs, including miR-124 and miR-107, thereby dysregulating downstream targets. It facilitates PINK1 degradation and potentially drives mitochondrial dysfunction and neuronal injury. Elevated NEAT1 levels are associated with amyloid-beta accumulation, tau hyperphosphorylation, and NF-κB-mediated neuroinflammation. Preclinical studies suggest that modulating NEAT1 expression can alleviate AD‑like pathology, making NEAT1 a promising target for intervention. Increased plasma NEAT1 in patients indicates its value as a non-invasive early diagnostic biomarker. NEAT1 regulates multiple AD-related pathways, including IGF1R, TRAF2, BACE1, CREB/BDNF, and Nrf2/NQO1, and interacts with lncRNAs linked to metabolic and neurodegenerative diseases, such as XIST and KCNQ1OT1. By influencing amyloid processing, synaptic function, mitochondrial health, and inflammatory responses, NEAT1 emerges as a central regulator in AD. Targeting NEAT1 offers dual benefits: advancing precision diagnostics and enabling multi-pathway therapeutic approaches. This review underscores NEAT1's significance as both a biomarker and therapeutic target, providing insights for future strategies to mitigate the burden of AD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611015","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":"Decreased Anti-inflammatory IL-2 and IL-10 and Increased Mononuclear Cell Tissue Factor Correlate with Stroke Severity: Do Anti-inflammatory Cytokines Modulate Thrombosis?","authors":"Kiana Mohammadian, Tahereh Kalantari, Rasoul Ebrahimi, Nahid Nasiri, Parisa Alipour, Gholamreza Rafiei Dehbidi, Afshin Borhani-Haghighi","doi":"10.2174/0118715273434957260202115619","DOIUrl":"https://doi.org/10.2174/0118715273434957260202115619","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory and coagulation pathways are crucial in the pathogenesis and clinical progression of ischemic stroke. The objective of this study was to evaluate serum concentrations of interleukin-2 (IL-2) and interleukin-10 (IL-10), as well as the gene expression of tissue factor (TF) in peripheral blood mononuclear cells (PBMCs), and to examine their correlations with stroke severity and clinical outcomes.</p><p><strong>Materials and methods: </strong>We enrolled 148 patients with ischemic stroke and 30 healthy controls matched for age and sex in a cross-sectional design. We used ELISA to measure the levels of IL-2 and IL-10 in serum and real-time PCR to look at TF gene expression in PBMCs. The NIH Stroke Scale (NIHSS) was used to measure the severity of strokes, and the results were compared to clinical variables.</p><p><strong>Results: </strong>Patients with severe stroke showed significantly lower levels of IL-2 and IL-10 (p < 0.001), and TF expression in PBMCs was significantly higher in both mild and severe stroke groups compared to controls (p < 0.001). There was no statistically significant difference between the mild and severe groups (p = 0.213). In severe cases, IL-2 and TF were negatively correlated (p = 0.036). Nonetheless, none of the biomarkers independently forecasted survival outcomes.</p><p><strong>Discussion: </strong>The results show that the immune-coagulation axis is not working properly in severe ischemic stroke. Lower levels of IL-2 and IL-10 may indicate that regulatory T-cells aren't working properly and that anti-inflammatory control isn't working, which can cause monocytes to become active and TF levels to rise. This interaction probably makes thromboinflammatory cascades worse, which leads to more damage to the nervous system. These changes, even though they don't predict survival, give us a better understanding of how strokes work and open up new possibilities for targeted immunomodulatory therapy.</p><p><strong>Conclusion: </strong>The changes in IL-2, IL-10, and TF expression indicate a coordinated disruption of immune and thrombotic pathways in individuals with severe ischemic stroke. Although not prognostic of mortality, these biomarkers may indicate disease severity and represent potential targets for future therapeutic interventions. Longitudinal studies are necessary to validate their prognostic significance and investigate their incorporation into clinical decision-making algorithms for stroke.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610944","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":"Targeting Blood-Brain Barrier Damage with Nanotechnology in the Fight Against Neurodegenerative Diseases.","authors":"V Rajeshwar, C Ronald Darwin, K Ilango, V T Iswariya, Shaik Shafiya Begum, Vasanth Kumar Mohan","doi":"10.2174/0118715273433580260209213317","DOIUrl":"https://doi.org/10.2174/0118715273433580260209213317","url":null,"abstract":"<p><p>The global health burden is attributed to neurodegenerative diseases, of which Alzheimer's disease and Parkinson's disease represent the major NDs. Changes in the blood-brain barrier system are considered an important mechanism in the pathogenesis of neurodegeneration, a process increasingly recognised. This review critically evaluates the recent advancement in nanotechnology that aims at targeting and recovering BBB disruption in neurodegenerative diseases. Nanoparticles, including polymeric, liposomal, micellar, metallic, and carbon-based systems, have the potential to cross the BBB. These mechanisms happen through receptor-mediated and adsorptive- mediated transcytosis. These nanoparticles also assist in repairing the BBB and allowing for protein expression. To counteract oxidative stress and alter inflammatory pathways. These nano systems are adept at drug control, neurovascular unit stability, and bioavailability enhancement of various medicines. Nanotechnology provides a dual advantage for therapy and active repairing. It can deliver drugs to the CNS selectively. The technology can actively repair the BBB structure and function. Further interdisciplinary research, translations, and safety assessments are essential to realize the full clinical promise of nanomedicine for the management of neurodegenerative diseases.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610941","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":"AI-Driven Biomarker Discovery in Motor-Related Neurodegenerative Diseases.","authors":"N Pavithra, Rukaiah Fatma Begum, S Thanga Ashwini, S Nirenjen, Anuragh Singh, M Manisha, S Sridevi, S Ankul Singh","doi":"10.2174/0118715273436955260126215111","DOIUrl":"https://doi.org/10.2174/0118715273436955260126215111","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxias (SCAs) are examples of neurodegenerative disorders (NDDs) that share overlapping neuropathological processes and largely affect motor coordination. For early diagnosis, illness monitoring, and treatment targeting, it is essential to find trustworthy biomarkers that represent motor circuit dysfunction. The purpose of this study is to summarize the state of the art regarding molecular, neurochemical, and imaging biomarkers that are pertinent to motor impairment and to investigate the function of artificial intelligence (AI) in their identification and verification Methods: With an emphasis on biomarker discovery, validation, and AI/ML applications in PD, HD, ALS, and SCAs, a thorough literature search was carried out in the PubMed, Scopus, and Google Scholar databases for research published between 2015 and 2025. The motor-specific correlations of key molecular (α-synuclein, tau, neurofilament light chain, TDP-43, mutant huntingtin), neuroimaging, and digital biomarkers were carefully examined Results: AI-driven methods, such as deep learning and machine learning, have shown great promise in combining multimodal data from digital, fluid, and imaging sources. These techniques enhanced the detection of disease-specific biomarker signatures, especially those associated with deficiencies in motor coordination Discussion: Data heterogeneity, biomarker standardization, model interpretability, and limited cross-disease validation are still issues despite encouraging developments. Improving the clinical reliability of AI-based biomarker models requires filling in these gaps Conclusion: An effective foundation for deciphering intricate motor neurological pathways is provided by AI-assisted biomarker discovery. Transparent algorithms, multicenter data integration, and ethical frameworks should be given top priority in future research to guarantee clinical translation and better patient stratification.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610936","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 Mechanisms of Ginsenosides in Spinal Cord Injury: A Systematic Review of Preclinical Evidence.","authors":"Yimin Yang, Jianxing Guo, Guowei Ye, Nan Li","doi":"10.2174/0118715273452620260123064249","DOIUrl":"https://doi.org/10.2174/0118715273452620260123064249","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) leads to severe sensory, motor, and autonomic dysfunction with limited treatment options. Ginsenosides, the primary bioactive compounds derived from Panax ginseng, have demonstrated neuroprotective potential in SCI. This systematic review aims to evaluate the preclinical evidence regarding the multi-target mechanisms of ginsenosides in SCI Methods: A comprehensive literature search was conducted following PRISMA guidelines across PubMed, Web of Science, and Google Scholar up to January 2025. Of the 385 identified articles, 22 studies met the inclusion criteria, which focused on the pharmacological effects of ginsenosides in SCI using both in vivo and in vitro models. Data on mechanisms, models, and outcomes were systematically synthesized Results: Ginsenosides exerted multi-target neuroprotective effects in SCI models, including antiinflammatory actions via suppression of TLR4/NF-κB and MAPK signaling, leading to reduced TNF-α, IL-1β, and IL-6, antioxidant activity through Nrf2/HO-1 pathway activation, enhancing SOD, CAT, and GSH, anti-apoptotic effects via ASK1/JNK inhibition, lowering caspase-9/3 and Bax while elevating the Bcl-2/Bax ratio, regulation of autophagy by activating PI3K/Akt to prevent excessive self-digestion, promotion of neural repair through upregulation of neurotrophic factors (NGF, bFGF, BDNF, and GDNF) and extracellular matrix components (laminin, fibronectin), inhibition of spinal cord edema via increased AQP4 expression, and facilitation of nerve regeneration by promoting astrocyte-to-neuron conversion and olfactory ensheathing cell migration Discussion: The findings highlight the synergistic mechanisms of ginsenosides in addressing key pathological processes in SCI, including inflammation, oxidative stress, apoptosis, and impaired neural regeneration. While preclinical evidence underscores their therapeutic promise, the translational potential requires validation through rigorous clinical trials to confirm efficacy, safety, and applicability in humans Conclusion: Ginsenosides exhibit multi-target neuroprotective effects in SCI models, positioning them as promising candidates for therapeutic development. Further clinical studies are essential to advance their application in SCI treatment.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610925","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":"Solid Lipid Nanoparticle Mediated Intranasal Drug Delivery for Brain Targeting: A Comprehensive Review.","authors":"Vaishali Kaushal, Abdul Hafeez, Shazia Afzal Usmani, Shafat Alam","doi":"10.2174/0118715273422409260129045318","DOIUrl":"https://doi.org/10.2174/0118715273422409260129045318","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) restricts the passage of drugs into the brain, preventing drug transport to the central nervous system and minimizing the therapeutic effectiveness of several drugs used for brain diseases. The intranasal route of administration provides a non-invasive, quick, and efficient means of achieving direct brain targeting. The anatomy and physiology of the nasal cavity play a vital role in drug absorption and transport to the brain. The olfactory and trigeminal nerves are directly linked to the brain, allowing drugs to bypass the BBB. Solid Lipid Nanoparticles (SLNs) have emerged as a potential drug delivery system for the intranasal administration of therapeutic agents targeting brain diseases. SLNs are composed of biocompatible lipids and surfactants and offer unique advantages, such as controlled drug release, enhancement in bioavailability, and high brain targeting potential. This review focuses on the exploration of drug-loaded intranasally delivered SLNs for brain diseases (Alzheimer's, Huntington's, stroke, epilepsy, depression, meningitis, Parkinsonism, migraine, brain cancer) with emphasis on the in vitro and in vivo findings. In the reviewed literature, the size of drug-loaded SLNs for brain delivery via intranasal administration was found to be in the range of 65-210 nm. Ongoing clinical trials and patents involving SLNs for intranasal delivery further strengthen the enhanced interest in this drug delivery platform for the effective management of brain diseases.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610992","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":"Biotechnological Perspectives on GSK-3β and Hyperprolactinemia: Implications for the Progression of Alzheimer's Disease.","authors":"Sudharshanan Jothi Venkatesan, Meghana Devraj, Mallesh Gowda Virupakshappa, Sonal Dubey, Sunil Kumar Kadiri, Prashant Tiwari","doi":"10.2174/0118715273426658260123115446","DOIUrl":"https://doi.org/10.2174/0118715273426658260123115446","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is a progressive neurodegenerative condition, which is typified by the extracellular presence of amyloid-B (A2) in the form of plaques, intracellular neurofibrillary tangles, which are made up of hyperphosphorylated tau, and deterioration of mental abilities. Glycogen synthase kinase-3 beta (GSK-3β) is also one of the molecular drivers that have been implicated in AD pathogenesis due to its contributions to tau hyperphosphorylation, Aβ production, and synaptic dysfunction. There is accumulating evidence suggesting that endocrine dysregulation and hyperprolactinemia, characterized by elevated circulating prolactin levels, may contribute to neurodegeneration through dopaminergic imbalance, oxidative stress, and neuroinflammation Methods: Recent peer-reviewed literature on the mechanistic intersections of GSK-32 signaling, hyperprolactinemia, and AD pathology was reviewed through a narrative synthesis. The research assessing hormonal regulation of neuroinflammatory cascades, dopaminergic tone, and structural changes in the brain was reviewed to identify potentially realistic biological relationships Results: It was found that inhibitory control of GSK-3b could be reduced by hyperprolactinemiainduced dopamine depletion, leading to increased GSK-3 b activity. This deregulation may increase tau phosphorylation and inflammatory reactions, which develop AD disease. Also, prolactinmediated oxidative stress may impair neuronal integrity Discussion: Hormonal imbalance and dysregulation of kinases are attractive therapeutic targets. Dopamine agonists can potentially reestablish dopaminergic suppression of GSK-3 2, whereas GSK-3 2 inhibitors have the potential to directly suppress tau pathology. A dual-modality approach can be beneficial in synergy, as it considers not only the neuroendocrine dimensions of AD but also the neurodegenerative Conclusion: Hyperprolactinemia may be an under-researched factor in the pathogenesis of AD. This clarification would guide the development of biomarkers and new, stratified interventions capable of going beyond traditional amyloid- and tau-based interventions.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610952","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":"Acute Effects of High-Intensity Interval Training (HIIT) on Heart Rate Variability and Psychoaffective Responses Among Bipolar Patients and their Control Peers: A Randomized Crossover Trial.","authors":"Alberto Souza Sá Filho, Marcelo Magalhães Sales, Pedro Augusto Inacio, Gaspar R Chiappa, Vicente Aprigliano, Rodolfo P Vieira, Iransé Oliveira-Silva, James Oluwagbamigbe Fajemiroye, Adrielle Beze Peixoto, Antônio Sérgio Nakao de Aguiar, Rodrigo Alvaro Brandão Lopes-Martins, Sergio Machado","doi":"10.2174/0118715273419942260117205457","DOIUrl":"https://doi.org/10.2174/0118715273419942260117205457","url":null,"abstract":"<p><strong>Introduction: </strong>to evaluate the acute effects of continuous moderate-intensity aerobic exercise and high-intensity interval training (HIIT) on heart rate variability (HRV) and psychoaffective responses in patients with bipolar disorder (BD) and healthy controls.</p><p><strong>Methods: </strong>Eight BD patients and eight controls underwent baseline assessments, including anthropometric measurements and a submaximal exercise test to determine VO2Max, followed by two randomized exercise sessions. In one session, participants performed 12 min of continuous exercise at 65%VO2Max, and in the other, during the HIIT protocol, participants engaged in six 45-s bouts at 100%VO2Max, each followed by a 1-min and 15-s recovery period at 40%VO2Max. Pre- and postexercise measurements included psychoaffective scales (feeling scale - FS, felt arousal scale - FAS, and SUDs anxiety scale) and HRV assessments recorded during a 10-minute rest period under controlled conditions.</p><p><strong>Results: </strong>Regarding RMSSD, both participants and sessions demonstrated a significant increase in this indicator (p=0.012). The BD significantly increased VLF and LF values and reduced HF values for both exercise sessions. Meanwhile, the LF/HF ratio showed a significant increase only in the HIIT session. For the control group, only a significant reduction in the HF index in both sessions and an increase in the LF/HF ratio only in the HIIT session. The FAS showed significant increases in bodily activation post-exercise across groups and modalities, while the FS demonstrated significant positive shifts in affective valence, with larger improvements following HIIT. Both exercise protocols produced significant reductions in anxiety levels (p=0.001), with HIIT showing a trend toward superior anxiolytic effects in BD patients.</p><p><strong>Discussion: </strong>The improvement in vagal tone and HRV modulates the function of critical brain regions involved in emotional regulation, such as the prefrontal cortex, amygdala, and anterior cingulate cortex. This modulation reduces limbic hyperactivity and impulsivity while influencing monoaminergic pathways, attenuating excessive dopaminergic signaling, thereby contributing to enhanced mood stability and the reduction of affective disturbances in individuals with BD.</p><p><strong>Conclusion: </strong>Both continuous moderate-intensity exercise and HIIT elicited favorable acute autonomic and psychoaffective responses in BD patients and healthy controls. Notably, HIIT tended to produce greater affective and anxiolytic benefits in individuals with BD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517753","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}