全部最新文献

{"title":"Translational challenges in amyotrophic lateral sclerosis therapy with macrophage migration inhibitory factor.","authors":"Leenor Alfahel, Aleksandar Rajkovic, Adrian Israelson","doi":"10.4103/NRR.NRR-D-24-00616","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00616","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein E elicits target-directed miRNA degradation to maintain neuronal integrity.","authors":"Jiazi Tan, Chin-Tong Ong","doi":"10.4103/NRR.NRR-D-24-00680","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00680","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems.","authors":"Alena Salasova, Anders Nykjær","doi":"10.4103/NRR.NRR-D-24-00734","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00734","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain.","authors":"Xiaoyu Zhang, Yuqi Liu, Fangxia Xu, Chengcheng Zhou, Kaimei Lu, Bin Fang, Lijuan Wang, Lina Huang, Zifeng Xu","doi":"10.4103/NRR.NRR-D-23-01539","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-23-01539","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202509000-00029/figure1/v/2024-11-05T132919Z/r/image-tiff Protein arginine methyltransferase-6 participates in a range of biological functions, particularly RNA processing, transcription, chromatin remodeling, and endosomal trafficking. However, it remains unclear whether protein arginine methyltransferase-6 modifies neuropathic pain and, if so, what the mechanisms of this effect. In this study, protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model, chronic constriction injury model and bone cancer pain model, using immunohistochemistry, western blotting, immunoprecipitation, and label-free proteomic analysis. The results showed that protein arginine methyltransferase-6 mostly co-localized with β-tubulin III in the dorsal root ganglion, and that its expression decreased following spared nerve injury, chronic constriction injury and bone cancer pain. In addition, PRMT6 knockout (Prmt6-/-) mice exhibited pain hypersensitivity. Furthermore, the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression. Moreover, when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury, increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn, and the response to mechanical stimuli was enhanced. Mechanistically, protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F. Additionally, protein arginine methyltransferase-6-mediated modulation of heterogeneous nuclear ribonucleoprotein-F expression required amino acids 319 to 388, but not classical H3R2 methylation. These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target for the treatment of peripheral neuropathic pain.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel method for clustering cellular data to improve classification.","authors":"Diek W Wheeler, Giorgio A Ascoli","doi":"10.4103/NRR.NRR-D-24-00532","DOIUrl":"10.4103/NRR.NRR-D-24-00532","url":null,"abstract":"<p><p>Many fields, such as neuroscience, are experiencing the vast proliferation of cellular data, underscoring the need for organizing and interpreting large datasets. A popular approach partitions data into manageable subsets via hierarchical clustering, but objective methods to determine the appropriate classification granularity are missing. We recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within clusters. Here we present the corresponding protocol to classify cellular datasets by combining data-driven unsupervised hierarchical clustering with statistical testing. These general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values, including molecular, physiological, and anatomical datasets. We demonstrate the protocol using cellular data from the Janelia MouseLight project to characterize morphological aspects of neurons.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between androgen signaling and the chemokine receptor CXCR4: a novel strategy to promote myelin regeneration.","authors":"Marianne Bardy-Lagarde, Narimène Asbelaoui, Abdel Mouman Ghoumari","doi":"10.4103/NRR.NRR-D-24-00439","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00439","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced autophagic clearance of amyloid-β via histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo.","authors":"Zhimin Long, Chuanhua Ge, Yueyang Zhao, Yuanjie Liu, Qinghua Zeng, Qing Tang, Zhifang Dong, Guiqiong He","doi":"10.4103/NRR.NRR-D-23-01633","DOIUrl":"10.4103/NRR.NRR-D-23-01633","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202509000-00025/figure1/v/2024-11-05T132919Z/r/image-tiff Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-β in neurons, which is a key step in senile plaque formation. Therefore, restoring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease. Microtubule acetylation/deacetylation plays a central role in lysosomal acidification. Here, we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease. Furthermore, we found that treatment with valproic acid markedly enhanced autophagy, promoted clearance of amyloid-β aggregates, and ameliorated cognitive deficits in a mouse model of Alzheimer's disease. Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease, in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of neuronal actin barrier promotes the entry of disease-implicated proteins to exacerbate amyotrophic lateral sclerosis pathology.","authors":"Mikito Shimizu, Tatsusada Okuno","doi":"10.4103/NRR.NRR-D-24-00661","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00661","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice.","authors":"Yujia Liu, Xue Han, Yan Su, Yiming Zhou, Minhui Xu, Jiyan Xu, Zhengliang Ma, Xiaoping Gu, Tianjiao Xia","doi":"10.4103/NRR.NRR-D-23-01233","DOIUrl":"10.4103/NRR.NRR-D-23-01233","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202509000-00032/figure1/v/2024-11-05T132919Z/r/image-tiff Postoperative cognitive dysfunction is a severe complication of the central nervous system that occurs after anesthesia and surgery, and has received attention for its high incidence and effect on the quality of life of patients. To date, there are no viable treatment options for postoperative cognitive dysfunction. The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research. To identify the signaling mechanisms contributing to postoperative cognitive dysfunction, we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset, which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus 3 days after tibial fracture. The dataset was enriched in genes associated with the biological process \"regulation of immune cells,\" of which Chil1 was identified as a hub gene. Therefore, we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fracture surgery. Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 1 24 hours post-surgery, and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests. In addition, protein expression levels of proinflammatory factors (interleukin-1β and inducible nitric oxide synthase), M2-type macrophage markers (CD206 and arginase-1), and cognition-related proteins (brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B) were measured in hippocampus by western blotting. Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment, downregulated interleukin-1β and nducible nitric oxide synthase expression, and upregulated CD206, arginase-1, pNR2B, and brain-derived neurotropic factor expression compared with vehicle treatment. Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1. Collectively, our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus. Therefore, recombinant chitinase-3-like protein 1 may have therapeutic potential for postoperative cognitive dysfunction.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology.","authors":"Yiyang Qin, Wenzhen Zhu, Tingting Guo, Yiran Zhang, Tingting Xing, Peng Yin, Shihua Li, Xiao-Jiang Li, Su Yang","doi":"10.4103/NRR.NRR-D-23-01666","DOIUrl":"10.4103/NRR.NRR-D-23-01666","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202509000-00027/figure1/v/2024-11-05T132919Z/r/image-tiff Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene, which encodes a ligand-dependent transcription factor. The mutant androgen receptor protein, characterized by polyglutamine expansion, is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients. These aggregates alter protein-protein interactions and compromise transcriptional activity. In this study, we reported that in both cultured N2a cells and mouse brain, mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-derived neurotrophic factor. Overexpression of mesencephalic astrocyte-derived neurotrophic factor ameliorated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation. Conversely, knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation. Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}