Cellular and Molecular Neurobiology最新文献

{"title":"Narrative Review \"Dual Frontiers in Neurodegeneration: Pharmacological Synergies and Divergences in Parkinson's Disease and Type 2 Diabetes Mellitus\".","authors":"Omnya A Sharallah, Vishnu Malakar, Ahmed E Salama, Salma M Elmaaz, Salma A Daba, Nitesh Kumar Poddar","doi":"10.1007/s10571-026-01702-0","DOIUrl":"10.1007/s10571-026-01702-0","url":null,"abstract":"<p><p>Diabetes mellitus (DM) and Parkinson’s disease (PD) are both chronic diseases that have a bidirectional relationship, wherein DM increases the risk of developing PD. Both diseases are related through overlapping pathways, insulin resistance, oxidative stress, and chronic inflammation, which can potentially lead to neurodegeneration. Insulin resistance and impaired insulin signalling present in DM may exacerbate neurodegeneration in PD. Current treatments for PD and DM can interact, such that dopaminergic drugs used to manage PD may increase the risk of altering glucose uptake, leading to exacerbated insulin resistance. Conversely, anti-diabetic drugs like GLP-1 receptor agonists and metformin may even be neuroprotective. However, not all anti-diabetic drugs provide utility in managing PD symptoms; some merely provide general metabolic change. The interplay between PD and DM remains largely uncharacterized, and due to the overlapping nature of these conditions, expanding the scope of research into novel and/or personalized causes of their combined effects may improve treatment efficacy.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hypothesis-Generating Pharmacologic Profile for Sargramostim Treatment of Parkinson's Disease.","authors":"Susmita Sil, Xiaoqing Du, Samia Akter, Mohit Kumar, Davina B Oludipe, Arnab Saha, Guoku Hu, Katie R Ostlund, Gleb R Haynatzki, Pamela Santamaria, R Lee Mosley, Howard E Gendelman","doi":"10.1007/s10571-026-01717-7","DOIUrl":"10.1007/s10571-026-01717-7","url":null,"abstract":"<p><p>The connection between immunity and Parkinson’s disease (PD) is well-established. Myeloid immune responses influence the microenvironment of the central nervous system (CNS), which can be modulated by sargramostim, a recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Previous studies have demonstrated sargramostim’s neuroprotective effects, which are linked to its safety and tolerability, as well as its ability to regulate innate immunity. Changes in myeloid biomarkers correlate with clinical responses. PD symptoms were assessed using the Unified PD Rating Scale (UPDRS). Ten subjects received sargramostim through subcutaneous injections of 3 µg/kg, administered five days every week. Myeloid biomarkers were measured before treatment and at six and twelve months of treatment. Protein expression by Western blotting and gene expression by transcriptomic analysis was correlated with UPDRS III scores. Recognizing the exploratory nature of this study, patient responses were classified into potent, moderate, or no change groups based on UPDRS III score reductions of 9–13, 5–7, or none, respectively. Biomarkers from all 10 patients identified FOXP3 as a “potential” signature biomarker. The potent responders showed biomarkers linked to autophagy, inflammatory, and antioxidant proteins, including ATG7, HMOX1, RELA, and TLR8. Moderate responders displayed biomarkers associated with RELA and LRRK2. Transcriptomic analysis revealed over 2000 differentially expressed anti-inflammatory, calcium-binding, and epigenetic genes. Among these, genes such as ANXA9, CALM3, CY7B1, HDAC4, HMGB2, NR2F6, PDIA3, REST, SACS and SOX4 were identified as potential predictors of changes in UPDRS III scores. Baseline levels of ATG7, CARD9, and SACS may serve as initial biomarkers to identify subjects likely to respond to sargramostim. Female patients exhibited unique UPDRS III scores in response to sargramostim treatment. Novel cell-based biomarker signatures were identified that may predict responses to sargramostim treatment in this hypothesis-generating study. We acknowledge the inherent study limitations by limited patient numbers. This was reflected in the comparisons offered for the patient sub-groups in the year-long trial.Trial Registration The trial is registered on ClinicalTrials.gov under identifier NCT03790670, dated 01.30.2019.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Mechanisms Regulating Ferroptosis in Ischemic Stroke: From Pathogenesis to Therapeutic Targets.","authors":"Jiale Gan, Xinyi Yang, Jianan Wu, Ziyan Cai, Xianglong Zhai, Yang Wu, Wenlei Li, Minghua Wu","doi":"10.1007/s10571-026-01718-6","DOIUrl":"10.1007/s10571-026-01718-6","url":null,"abstract":"<p><p>Ischemic stroke (IS) remains a leading cause of death and disability worldwide; however, effective neuroprotective therapies are lacking. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key contributor to neuronal injury following cerebral ischemia. Epigenetic mechanisms, including DNA methylation, histone modification, and microRNA (miRNA) regulation, critically modulate ferroptosis-related gene expression. This review systematically examines how epigenetic modifications regulate ferroptosis in IS by influencing iron homeostasis, antioxidant defense systems, and lipid metabolism. We highlighted key regulatory axes, such as DNMT-mediated GPX4 and PINK1 methylation, HDAC-regulated iron uptake and antioxidant defense, ubiquitination-dependent SLC7A11 and ACSL4 regulation, and miRNA/ferroptosis-related targets. Furthermore, we discuss the therapeutic potential of targeting these epigenetic-ferroptosis interactions for IS treatment. Understanding these mechanistic links may facilitate the development of novel epigenetic-based strategies to inhibit ferroptosis and improve the outcomes of patients with IS.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13062076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on Spinal Cord Repair Based on Regulation of the Neuroregenerative Microenvironment.","authors":"Zixiang Deng, Huijie Zhang, Xiaoyu Li, Yongbin Feng, Yang Liu, Hanfei Shang, Ming Li, Xiaoyi Zhou, Xianzhao Wei","doi":"10.1007/s10571-026-01711-z","DOIUrl":"10.1007/s10571-026-01711-z","url":null,"abstract":"<p><p>Spinal cord injury is a disease with no complete cure. It typically results in loss of motor and sensory functions below the level of the lesion, leading to significant physical and psychological disorders. After spinal cord injury, the microenvironmental balance at the site of injury is disrupted, creating complex conditions that are not conducive to nerve regeneration and recovery of spinal cord function, such as hemorrhage and ischemia, glial scar formation, and nerve demyelination. As our knowledge of the spinal cord microenvironment has expanded, researchers have determined that therapeutic strategies that modulate the microenvironment represent a significant and efficacious avenue of investigation. This review summarizes the characteristics of microenvironmental changes at various stages after spinal cord injury. Additionally, it discusses novel strategies developed recently based on regulating the microenvironment after spinal cord injury to promote recovery. The investigation of a long-acting, targeted, and multitemporal combination therapy strategy to repair spinal cord injuries shows promise in terms of its developmental potential.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Non-viral Delivery of Genes to Central Nervous System Disorders.","authors":"Hany E Marei","doi":"10.1007/s10571-026-01703-z","DOIUrl":"10.1007/s10571-026-01703-z","url":null,"abstract":"<p><p>Disorders of the central nervous system (CNS), neurological disorders, neurodegenerative disorders, genetic disorders) constitute a significant burden on global health, and current treatment options remain challenging. As treatment for CNS disorders is primarily palliative, the underlying causes of disease progression are not addressed through conventional pharmacologic therapies. Gene therapy has the potential to address these root causes of disease progression; however, many of the vectors used in gene therapy (e.g., adeno-associated viruses (AAVs)) have limitations such as immunogenicity, low cargo capacity, and crossing the blood-brain barrier (BBB). These limitations have led to significant progress in the development of non-viral gene delivery systems. Compared with viral vectors, non-viral platforms offer improved safety profiles, greater design flexibility, lower production costs, and superior suitability for repeated administration. This review reports recent advancements in the development of non-viral platforms for CNS gene delivery and focuses on lipid-based nanoparticles, polymeric nanoparticles, exosome-based techniques, and new hybrid technologies. Particular emphasis is placed on nanoparticle modification approaches to enhance BBB penetration and enable delivery of genome-editing technologies (CRISPR/Cas systems). The review provides explanations of clinical trials, regulatory considerations, and manufacturing issues that result from the recent developments noted above. It also explores the emerging role of artificial intelligence in supporting carrier design and enhancing delivery efficiency. Both artificial intelligence and non-viral platforms have the potential to facilitate the advancement of safe, effective, and repeatably administered gene therapies for patients with CNS disorders.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA Damage in Substantia Nigra Pars Compacta Astrocytes Exacerbates Dopaminergic Neuron Loss in a 6-Hydroxydopamine Mouse Model of Parkinsonism.","authors":"Daniela A Ayala, Grace M Hall, Debanjana Das, Eliana Tijerina, Luisa Lopez Villagran, Zaid Khan, Devanshi Paliwal, Anu Anand, Mendell Rimer, Rahul Srinivasan","doi":"10.1007/s10571-026-01713-x","DOIUrl":"10.1007/s10571-026-01713-x","url":null,"abstract":"<p><p>Parkinson’s disease (PD) is the fastest growing neurological disorder with no known cure. Our ability to develop disease-modifying treatments that slow down the loss of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is hindered by a dearth of knowledge on roles for non-neuronal elements such as astrocytes during PD pathogenesis. More specifically, the extent to which mitochondrial DNA (mtDNA) damage in SNc astrocytes contributes to SNc DA neuron loss during PD remains unknown. To address this knowledge gap, we utilized an adeno-associated virus (AAV) called Mito-PstI that expresses the restriction enzyme PstI as an approach to damage mtDNA in SNc astrocytes and assess the effect of astrocytic mtDNA damage on SNc DA neuron function and viability in mice. Mito-PstI-induced mtDNA damage in SNc astrocytes increased the density of S100B-containing astrocytic processes in the SNc and abnormally increased dopamine release by SNc DA neuron axonal terminals within the dorsolateral striatum (DLS). In addition, mice injected with Mito-PstI in the SNc showed increased spontaneous and apomorphine-induced rotations contralateral to the side with SNc Mito-PstI injections. In further experiments, we used a parkinsonian mouse model with low dose 6-hydroxydopamine (6-OHDA) injection into the DLS to show that Mito-PstI expression in SNc astrocytes caused a worsening of 6-OHDA-induced spontaneous contralateral rotational behavior, and exacerbated SNc DA neuron loss. These results suggest that mitochondria in SNc astrocytes are not only critical for the function of SNc DA neurons, but are also a new target for developing disease-modifying strategies against PD.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.","authors":"Yaxin Shang, Binglin Kuang, Jia Zheng, Yunpeng Du, Tong Shang, Baochun Luo, Yue Sun, Lei Zheng, Baiwen Zhang, Li Liu, Wei Zou","doi":"10.1007/s10571-026-01675-0","DOIUrl":"10.1007/s10571-026-01675-0","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular disease, which is an important cause of death and disability. Accumulating evidence indicates that the neutrophil extracellular traps (NETs) and complement cascade play an important role in the injury after ICH. Neutrophils, the first leukocyte subset recruited to the cerebral parenchyma following ICH, exacerbate cerebral tissue damage via the release of NETs. As a core component of the innate immune system, the complement system aggravates cerebral edema and pathological injury after ICH through a variety of complex pathological processes. Some complement molecules, such as C5a, C3a, and C1q, are associated with increased neutrophil recruitment and NETs release. Therefore, this review summarized the formation of NETs and activation of complement, the role of NETs and complement in ICH, the interaction between NETs and complement, and related treatment methods, providing new therapeutic strategies for clinical treatment.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay Between Autophagy, Cellular Senescence, and Brain Aging: Neuroprotective Implications of Intermittent Fasting.","authors":"Ishika Singh, Shreya Bhat, Rajesh Tamatta, Abhishek Kumar Singh","doi":"10.1007/s10571-026-01709-7","DOIUrl":"10.1007/s10571-026-01709-7","url":null,"abstract":"<p><p>Aging is characterized by progressive deterioration in cellular function and molecular integrity, which in turn increases vulnerability to age-related diseases, such as neurodegenerative disorders. Cellular senescence is a hallmark of biological aging that plays a crucial role in the development of neurodegenerative diseases. Cellular autophagy, a lysosome-mediated process of degradation, is crucial for maintaining cellular homeostasis and longevity. Nutritional strategies, such as intermittent fasting (IF), which consist of cycles of fasting and normal feeding, have been recognized as potential methods to induce autophagy and derive health benefits. Autophagy is crucial for the degradation of sequestered proteins and damaged organelles, thus maintaining cellular vigor and balance. However, with increasing age, autophagy is compromised, suggesting the need for a stable or optimal rate of autophagy for the maintenance of cellular uptake. IF has the potential to modulate the process of autophagy by inducing changes in ATP and ADP levels during fasting through the activation of pathways such as the AMPK and Sirtuin 1 pathways, which promote the activation of autophagosome formation while simultaneously inhibiting mTOR, an inhibitor of autophagy. Despite the encouraging properties of the IF, there are constraints, as responses may vary incredibly among subjects, and the ideal duration of fasting is uncertain. Furthermore, the potential for new metabolic diseases associated with IF is not fully understood. Understanding the intricate relationships among aging, autophagy, and dietary restrictions such as intermittent fasting could pave the way for novel therapeutic strategies to increase longevity and mitigate age-related health issues.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Inflammatory Biomarkers in Parkinson's Disease: Clinical Correlations and Stratification.","authors":"Guo-Yun Jiang, Fan Li, Jin-Hui Yin, Ling-Xiao Cao","doi":"10.1007/s10571-026-01708-8","DOIUrl":"10.1007/s10571-026-01708-8","url":null,"abstract":"<p><p>Growing evidence underscores neuroinflammation's role in Parkinson's disease (PD), with accumulating evidence suggesting a potential role for peripheral inflammation. The clinical applicability and mechanistic relevance of peripheral inflammatory biomarkers in PD remain to be fully elucidated. We analyzed data from the Parkinson's Progression Markers Initiative (PPMI), including longitudinal clinical assessments, blood counts, cerebrospinal fluid (CSF) biomarkers, and genetic data. Six peripheral inflammatory indices were derived: neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). Spearman correlation, multiple linear regression, and generalized estimating equations were employed to examine associations. Unsupervised k-means clustering was performed to identify distinct inflammatory clusters, with differences assessed using ANCOVA analysis. NLR and SII were significantly elevated in PD, with NLR showing the strongest association. Peripheral inflammatory biomarkers showed distinct clinical correlations, with NLR demonstrating associations with both non-motor (cognitive decline, olfactory impairment, and depression, p < 0.001) and motor symptoms (p < 0.001). SII, and SIRI showed correlations with motor progression (p < 0.001), while SII additionally associated with sleepiness disorders (p < 0.001). Cluster analysis identified two distinct inflammatory clusters: a high-inflammation cluster demonstrating significantly worse cognitive function (p = 0.008), olfactory impairment (p < 0.001), and autonomic dysfunction (p < 0.001) at baseline, along with accelerated motor (p = 0.038) and cognitive decline (p < 0.001) during follow-up. This high-inflammation cluster also showed elevated CSF neurodegeneration markers including pTau, tTau, NfL, and GFAP (p < 0.05). Peripheral inflammatory biomarkers show robust associations with clinical features in PD, highlighting their potential as markers associated with disease features and progression, and suggesting a basis for inflammatory-based subgrouping.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric Oxide Donor Alleviates Cardiac Arrest Induced Blood Brain Barrier Injury by Inhibiting HMGB1-ATG5 Mediated Endothelial Autophagy.","authors":"Pengyu Duan, Yonghong Bi, Weiyu Feng, Zhehao Jin, Yao Meng, Hangbing Li, Xiaoyan Li, Lan Luo, Xiangcheng Zhao, Bing Zhang","doi":"10.1007/s10571-026-01706-w","DOIUrl":"10.1007/s10571-026-01706-w","url":null,"abstract":"<p><p>Cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) often cause severe neurological deficits due to ischemia–reperfusion (I/R) injury, marked by systemic inflammation, blood–brain barrier (BBB) dysfunction, and excessive autophagy. JS-K, a nitric oxide-releasing prodrug, has shown cytoprotective effects, but its role in CA-induced brain injury remains unclear. Here, we investigated the therapeutic potential of JS-K in a mouse CA/CPR model and an in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model. JS-K treatment improved neurological outcomes, preserved BBB function, and prolonged survival. Mechanistically, JS-K preserved tight junction proteins and improved BBB function and suppressed endothelial autophagy in vivo and in vitro. Further analyses revealed that HMGB1, after nuclear-cytoplasmic translocation, interacted with ATG5, inducing excessive autophagy and BBB injury. JS-K inhibited HMGB1 translocation, reduced HMGB1-ATG5 interaction, and consequently mitigated autophagy-driven BBB dysfunction. Notably, ATG5 silencing failed to enhance JS-K’s protective effects, supporting that JS-K acts at least in part through the HMGB1-ATG5 axis. These findings identify JS-K as a promising therapeutic agent that targets HMGB1-mediated autophagy to protect BBB function after cardiac arrest.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}