NeuroMolecular Medicine最新文献

{"title":"5-Repurposed Drug Candidates Identified in Motor Neurons and Muscle Tissues with Amyotrophic Lateral Sclerosis by Network Biology and Machine Learning Based on Gene Expression.","authors":"Kubra Temiz, Aytac Gul, Esra Gov","doi":"10.1007/s12017-025-08847-z","DOIUrl":"10.1007/s12017-025-08847-z","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to motor neuron degeneration, muscle weakness, and respiratory failure. Despite ongoing research, effective treatments for ALS are limited. This study aimed to apply network biology and machine learning (ML) techniques to identify novel repurposed drug candidates for ALS. In this study, we conducted a meta-analysis using 4 transcriptome data in ALS patients (including motor neuron and muscle tissue) and healthy controls. Through this analysis, we uncovered common shared differentially expressed genes (DEGs) separately for motor neurons and muscle tissue. Using common DEGs as proxies, we identified two distinct clusters of highly clustered differential co-expressed cluster genes: the 'Muscle Tissue Cluster' for muscle tissue and the 'Motor Neuron Cluster' for motor neurons. We then evaluated the performance of the nodes of these two modules to distinguish between diseased and healthy states with ML algorithms: KNN, SVM, and Random Forest. Furthermore, we performed drug repurposing analysis and text-mining analyses, employing the nodes of clusters as drug targets to identify novel drug candidates for ALS. The potential impact of the drug candidates on the expression of cluster genes was predicted using linear regression, SVR, Random Forest, Gradient Boosting, and neural network algorithms. As a result, we identified five novel drug candidates for the treatment of ALS: Nilotinib, Trovafloxacin, Apratoxin A, Carboplatin, and Clinafloxacin. These findings highlight the potential of drug repurposing in ALS treatment and suggest that further validation through experimental studies could lead to new therapeutic avenues.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"24"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780733","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":"Folic Acid Promotes Peripheral Nerve Injury Repair via Regulating DNM3-AKT Pathway Through Mediating Methionine Cycle Metabolism.","authors":"Weibo Kang, Yanli Zhang, Wei Cui, Hua Meng, Duo Zhang","doi":"10.1007/s12017-025-08845-1","DOIUrl":"10.1007/s12017-025-08845-1","url":null,"abstract":"<p><p>Emerging evidence suggests that folic acid (FA) supports nerve repair, but its beneficial effects in peripheral nerve injury (PNI) remains unclear. This study aims to investigate protective effects of FA against PNI and the underlying molecular mechanisms. High-performance liquid chromatography-tandem mass spectrometry was utilized for precise quantification of metabolites. A sciatic nerve crush injury model was established in rats, followed by assessments of cell proliferation, apoptosis, and motor function using CCK-8 assays, flow cytometry, and the balance beam test, respectively. Neuromorphological observations, electromyography, and ELISA were conducted to evaluate structural, electrophysiological, and biochemical parameters. In vitro, FA restored methionine cycle balance in Schwann cells and neurons disrupted by enzyme inhibition, improving cell viability, reducing apoptosis, and preserving cellular structure. In vivo, FA supplementation restored S-adenosylmethionine and homocysteine levels in a methionine metabolism disorder model and enhanced motor function, neural morphology, neuron survival, and electrophysiological recovery after PNI. Epigenetic analyses revealed that FA modulated DNA methylation and histone modifications of the DNM3 promoter, influencing gene expression. Furthermore, FA facilitated nerve repair via the DNM3-AKT pathway, regulating apoptosis, autophagy, and oxidative stress-related enzymes. These findings highlight FA's potential in promoting nerve repair through metabolic and epigenetic mechanisms.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"23"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753768","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 Role of G-Protein-Coupled Receptor Kinase 4 in Modulating Mitophagy and Oxidative Stress in Cerebral Ischemia-Reperfusion Injury.","authors":"Jian Wang, Diheng Gu, Ke Jin, Hualong Shen, Yaohua Qian","doi":"10.1007/s12017-025-08843-3","DOIUrl":"https://doi.org/10.1007/s12017-025-08843-3","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion injury (CIRI) causes significant neuronal damage through oxidative stress, inflammation, and mitochondrial dysfunction. The G-protein-coupled receptor kinase 4 (GRK4) has been implicated in regulating stress responses in various tissues, but its role in ischemic brain injury remains unclear. In this study, we investigated the role of GRK4 in oxidative stress, inflammation, and mitophagy during CIRI using both in vivo and in vitro models. For the in vivo experiments, we employed the bilateral common carotid artery occlusion (BCCAO) model to induce ischemia-reperfusion injury. Our finding demonstrated that ischemic reperfusion significantly upregulated GRK4 expression in the brain, correlating with elevated levels of inflammatory cytokines and oxidative stress markers. In cultured cerebellar neurons subjected to oxygen-glucose deprivation (OGD), over-expression of GRK4 decreased cell viability, while GRK4 inhibition enhanced neuronal survival, suggesting that GRK4 exacerbates neuronal damage in ischemic conditions. Furthermore, GRK4 overexpression impaired mitophagy, as indicated by altered expression of key mitophagy-related proteins (Beclin-1, PINK1, and p62), which led to mitochondrial dysfunction and increased oxidative stress. In contrast, GRK4 inhibition promoted more efficient mitophagy and improved mitochondrial quality control. These results highlight the detrimental role of GRK4 in ischemic brain injury and suggest that targeting GRK4 could offer a novel therapeutic strategy to mitigate neuronal damage by balancing oxidative stress, inflammation, and mitochondrial dynamics. Further studies are needed to elucidate the precise molecular mechanisms underlying GRK4-mediated neuroinflammation and mitochondrial dysfunction in ischemic stroke.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"21"},"PeriodicalIF":3.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SP3-Mediated Transcriptional Activation of GRIK1 is Involved in Alzheimer's Disease-Induced Cognitive Decline by Inducing Inflammasome Activation in Microglia.","authors":"Xiaolin Pang, Zhun Wang, Mengxue Zhang, Jinpeng Dong, Zhonglan Dong, Yiqing Yin","doi":"10.1007/s12017-025-08844-2","DOIUrl":"https://doi.org/10.1007/s12017-025-08844-2","url":null,"abstract":"<p><p>GRIK1 has been identified to suppress the activation of NLRP3 inflammasome. The present study investigated the damaging effect of GRIK1 on Alzheimer's disease (AD), the most common neurodegenerative disease, by focusing on inflammasome. APP-PS1 mice were subjected to a Y-maze test and a Morris water maze test. APP-PS1 mice with GRIK1 knockdown were constructed using adeno-associated virus, and the effects of GRIK1 knockdown on the NLRP3 inflammasome activation in microglia of brain tissues of APP-PS1 mice were analyzed. Mouse primary microglia BV2 was induced by LPS, and Western blot, flow cytometry, and ELISA were performed. GRIK1 was significantly elevated in the brain tissues of APP-PS1 mice. GRIK1 knockdown inhibited the neuronal damage and NLRP3 neuroinflammation in the brain tissues and improved cognitive dysfunction of APP-PS1 mice. Knockdown of GRIK1 inhibited activation of NLRP3 inflammasome in BV2 cells. SP3 was upregulated in the brain tissues of APP-PS1 mice, and SP3 promoted GRIK1 transcription by binding to its promoter. Overexpression of GRIK1 reversed the mitigating effect of knockdown of SP3 on cognitive dysfunction and NLRP3 activation in APP-PS1 mice. Overall, our results revealed that SP3-induced GRIK1 transcription potentiates NLRP3 inflammasome activation in microglia, leading to cognitive dysfunction in AD.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"22"},"PeriodicalIF":3.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Peripheral Amyloid-β Nexus: Connecting Alzheimer's Disease with Atherosclerosis through Shared Pathophysiological Mechanisms.","authors":"Manal M Khowdiary, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Ahmed A Elhenawy, Eman K Rashwan, Athanasios Alexiou, Marios Papadakis, Mohammed E Abo-El Fetoh, Gaber El-Saber Batiha","doi":"10.1007/s12017-025-08836-2","DOIUrl":"10.1007/s12017-025-08836-2","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and atherosclerosis (AS) are two chronic diseases with seemingly distinct pathologies. However, emerging research points to a bidirectional relationship driven by common mechanisms, such as inflammation, oxidative stress, and dysregulation of Amyloid-Beta (Aβ). This review focuses on the role of Aβ as a critical molecular link between AD and AS, emphasizing its contribution to neuronal impairment and vascular damage. Specifically, peripheral Aβ produced in the pancreas and skeletal muscle tissues exacerbates AS by promoting endothelial dysfunction and insulin resistance (IR). Furthermore, AS accelerates AD progression by impairing cerebral blood flow and inducing chronic hypoxia, causing Aβ accumulation. This review critically evaluates recent findings, highlighting inconsistencies in clinical studies and suggesting future research directions. Understanding the bidirectional influence of AD and AS could pave the way for novel therapeutic approaches targeting shared molecular pathways, particularly emphasizing Aβ clearance and inflammation.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"20"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542804","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":"Leptin and Leptin Signaling in Multiple Sclerosis: A Narrative Review.","authors":"Juan Antonio Flores-Cordero, Amalia Aranaz-Murillo, Teresa Vilariño-García, Antonio Pérez-Pérez, Guillermo Izquierdo, Rocío Flores-Campos, Lourdes Hontecillas-Prieto, Daniel J García-Domínguez, Víctor Sánchez-Margalet","doi":"10.1007/s12017-025-08842-4","DOIUrl":"10.1007/s12017-025-08842-4","url":null,"abstract":"<p><p>Obesity, a pandemic health problem, is now considered as a chronic inflammatory state, related to many autoimmune diseases, such as multiple sclerosis. Thus, adipokines, inflammatory mediators secreted by adipose tissue, play an important role modulating the immune response. In this context, obesity, especially during adolescent age, seems to be a key factor for the development of multiple sclerosis. Leptin, the main pro-inflammatory adipokine secreted by the adipose tissue, has been found increased in patients with multiple sclerosis and is able to regulate the immune system promoting a pro-inflammatory response. Leptin signaling in both innate and adaptative immune cells might have immunomodulatory effects in the context of multiple sclerosis. In this way, leptin has been found to produce a Th1 and Th17 response, increasing M1 macrophages and decreasing regulatory T cells and Th2 response. Moreover, circulating inflammatory adipokines, such as leptin, have been found in people with multiple sclerosis. In the present work, we are reviewing literature to update the body of knowledge regarding the role of obesity and leptin in multiple sclerosis.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"19"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523946","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":"NOTCH3 Variant Position Affects the Phenotype at the Pluripotent Stem Cell Level in CADASIL.","authors":"Ana Bugallo-Casal, Elena Muiño, Susana B Bravo, Pablo Hervella, Susana Arias-Rivas, Manuel Rodríguez-Yáñez, Enrique Vara-León, Rita Quintas-Rey, Lara Pérez-Gayol, Olga Maisterra-Santos, Jesús Pizarro-Gonzálvez, María Rosa Martorell-Riera, Cristòfol Vives-Bauzá, Israel Fernández-Cadenas, José Castillo, Francisco Campos","doi":"10.1007/s12017-025-08840-6","DOIUrl":"10.1007/s12017-025-08840-6","url":null,"abstract":"<p><p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic form of stroke. It is caused by a cysteine-altering variant in one of the 34 epidermal growth factor-like repeat (EGFr) domains of Notch3. NOTCH3 pathogenic variants in EGFr 1-6 are associated with high disease severity, whereas those in EGFr 7-34 are associated with late stroke onset and increased survival. However, whether and how the position of the NOTCH3 variant directly affects the disease severity remains unclear. In this study, we aimed to generate human-induced pluripotent stem cells (hiPSCs) from patients with CADASIL with EGFr 1-6 and 7-34 pathogenic variants to evaluate whether the NOTCH3 position affects the cell phenotype and protein profile of the generated hiPSCs lines. Six hiPSCs lines were generated: two from patients with CADASIL with EGFr 1-6 pathogenic variants, two from patients with EGFr 7-34 variants, and two from controls. Notch3 aggregation and protein profiles were tested in the established six hiPSCs lines. Cell analysis revealed that the NOTCH3 variants did not limit the cell reprogramming efficiency. However, EGFr 1-6 variant position was associated with increased accumulation of Notch3 protein in pluripotent stem cells and proteomic changes related with cytoplasmic reorganization mechanisms. In conclusion, our analysis of hiPSCs derived from patients with CADASIL support the clinical association between the NOTCH3 variant position and severity of CADASIL.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"18"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523950","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":"Annexin A's Life in Pan-Cancer: Especially in Glioma Immune Cells.","authors":"Yujing Wen, Wenhao Zhou, Zhenzhen Zhao, Didi Ma, Jian Mao, Yingjie Cai, Fugui Liu, Juan Zhou, Kun Lv, Wenchao Gu, Lan Jiang","doi":"10.1007/s12017-024-08827-9","DOIUrl":"https://doi.org/10.1007/s12017-024-08827-9","url":null,"abstract":"<p><p>The Annexin A (ANXA) family plays a critical role in cancer, with particular emphasis on their prognostic significance in pan-cancer analyses and gliomas. By integrating multi-omics data from The Cancer Genome Atlas (TCGA) and single-cell sequencing analysis, we conducted a comprehensive evaluation of ANXA2 and ANXA4 to investigate their expression patterns and functional impacts across various cancers, with a focus on glioblastoma (GBM). Our analysis encompassed several key components, including literature review, identification of differentially expressed genes (DEGs) in cancer, survival analysis, co-expression studies, competing endogenous RNA networks, cellular functional analysis, tumor microenvironment response to chemotherapy, and tumor stemness. Special attention was given to glioblastoma and low-grade glioma. Notably, our findings highlighted discrepancies among the analytical tools used, underscoring the necessity of employing multiple methods for accurate identification of DEGs. Additionally, we determined that ANXA2 and ANXA4 are predominantly expressed by M2 macrophages in GBM, based on our characterization of human glioma macrophages. These results suggest a strong correlation between ANXA2 and ANXA4 expression levels and the presence of macrophages and CD4 + resting memory T cells in gliomas, offering valuable insights into the complex interplay between the ANXA family and cancer progression.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"17"},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAR1 Promotes NUPR1 A-to-I RNA Editing to Exacerbate Ischemic Brain Injury by Microglia Mediated Neuroinflammation.","authors":"Guo-Ping Wang, Wen-Juan Li, Ye Li, Ming-Xing Ma, Kai-Kai Guo","doi":"10.1007/s12017-025-08841-5","DOIUrl":"10.1007/s12017-025-08841-5","url":null,"abstract":"<p><p>Microglial cells occupy a crucial position as potential therapeutic targets in the context of ischemic stroke (IS). Nonetheless, the intrinsic mechanisms that govern microglial activation in the aftermath of IS remain incompletely elucidated. ADAR1 p150 plays a significant role in immune regulation and stress responses; however, the specific pathways through which it modulates microglial activation and the subsequent mechanisms that unfold following IS have yet to be clearly delineated. The distal middle cerebral artery occlusion (dMCAO) mouse model was utilized to induce IS. The evaluation of infarct volume was conducted through TTC staining, while neurological function was assessed using the modified Neurological Severity Score (mNSS). To evaluate the expression of ADAR1 and apoptosis-related proteins, immunofluorescence and Western blot techniques were employed. BV2 cells were subjected to oxygen-glucose deprivation followed by reperfusion (OGD/R). Additionally, a co-culture system of BV2 cells and neurons was established, and subsequent assessments of neuronal viability and apoptosis were performed using CCK-8 assays and LDH release assays. ADAR1 p150 expression was significantly upregulated in the brains of ischemic mice, particularly within microglial cells. The overexpression of ADAR1 p150 was found to promote microglial activation and enhance pro-inflammatory responses, whereas the knockdown of ADAR1 p150 yielded the opposite effect. Additionally, the knockdown of ADAR1 p150 in microglia resulted in a marked reduction in neuronal apoptosis within the co-culture system. Rescue experiments indicated that the knockdown of NUPR1 partially reinstated the inflammatory response previously induced by ADAR1 p150 knockdown. Notably, ADAR1 p150 knockdown also inhibited A-to-I RNA editing while simultaneously upregulating NUPR1. Furthermore, the reduction of ADAR1 expression was associated with decreased infarct volume, improved neurological outcomes, and a significant attenuation of neuroinflammation in dMCAO mice. ADAR1 p150 enhances the microglial inflammatory response and neuronal apoptosis in IS by facilitating A to I RNA editing of NUPR1.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"16"},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of TUBB6 Inhibition for Hematoma Reduction, Microtubule Stabilization, and Neurological Recovery in an In Vivo Model of Intracerebral Hemorrhage.","authors":"Jun-Yao Huang, Qiang Ma, Ya-Jie Qi, Zhi-Yao Wang, Xiao-Guang Liu, Yi-Ming Zhu, Yu-Ping Li","doi":"10.1007/s12017-025-08838-0","DOIUrl":"https://doi.org/10.1007/s12017-025-08838-0","url":null,"abstract":"<p><p>This in vivo study explored the impact of TUBB6 inhibition in intracerebral hemorrhage (ICH), focusing on its effects on hematoma volume, microtubule stability, inflammation, neuronal preservation, and sensorimotor recovery. Sprague-Dawley rats was used to induce ICH by collagenase injection into the right striatum, followed by administration of TUBB6 antisense oligonucleotide (ASO) or Control ASO directly into the hematoma site 3 h post-ICH. Outcomes measured included hematoma volume, microtubule stability (acetylated α-tubulin), levels of inflammatory cytokines, mitogen-activated protein kinase (MAPK) pathway activity, neuronal degeneration (Fluoro-Jade C staining), and cell integrity (Cresyl Violet staining). Functional recovery was assessed using neurological severity scores (mNSS), corner turn, forelimb-placing, and rotarod tests, with body weight tracked for up to 28 days. TUBB6 expression increased with the severity of hemorrhage in the ICH models. TUBB6 ASO significantly reduced hematoma volume at 24- and 72-h post-ICH, restored acetylated α-tubulin levels, suppressed MAPK signaling pathway, and decreased pro-inflammatory markers with increased IL-10. TUBB6 ASO also reduced neuronal degeneration and improved cell viability. In terms of functional outcomes, the TUBB6 ASO + ICH group exhibited reduced mNSS scores, improved body weight maintenance, and better performance on corner turn, forelimb-placing and rotarod tests compared to the Control ASO + ICH group. TUBB6 ASO treatment demonstrated therapeutic potential in a rat model of ICH by reducing hematoma volume, stabilizing microtubules, modulating the MAPK signaling pathway, and mitigating inflammation. It also preserved neuronal integrity and enhanced sensorimotor recovery, suggesting its effectiveness as a therapeutic approach to improve ICH outcomes.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"15"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}