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{"title":"A single-cell landscape of the regenerating spinal cord of zebrafish.","authors":"Lei Yao, Xinyi Cai, Saishuai Yang, Yixing Song, Lingyan Xing, Guicai Li, Zhiming Cui, Jiajia Chen","doi":"10.4103/NRR.NRR-D-24-01163","DOIUrl":"10.4103/NRR.NRR-D-24-01163","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00046/figure1/v/2025-05-05T160104Z/r/image-tiff Unlike mammals, zebrafish possess a remarkable ability to regenerate their spinal cord after injury, making them an ideal vertebrate model for studying regeneration. While previous research has identified key cell types involved in this process, the underlying molecular and cellular mechanisms remain largely unexplored. In this study, we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish. Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury, while molecular signals promoting growth cone collapse were inhibited. Radial glial cells exhibited significant proliferation and differentiation potential post injury, indicating their intrinsic roles in promoting neurogenesis and axonal regeneration, respectively. Additionally, we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury, creating a microenvironment permissive for tissue repair and regeneration. Furthermore, oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury. These findings demonstrated that the rapid and orderly regulation of inflammation, as well as the efficient proliferation and redifferentiation of new neurons and glial cells, enabled zebrafish to reconstruct the spinal cord. This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration, offering promising avenues for future research and therapeutic strategies.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"780-789"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995473","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":"Unraveling the role of ufmylation in the brain.","authors":"Rita J Serrano, Robert J Bryson-Richardson","doi":"10.4103/NRR.NRR-D-24-01311","DOIUrl":"10.4103/NRR.NRR-D-24-01311","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"667-668"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006899","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":"Neural circuit mechanisms of epilepsy: Maintenance of homeostasis at the cellular, synaptic, and neurotransmitter levels.","authors":"Xueqing Du, Yi Wang, Xuefeng Wang, Xin Tian, Wei Jing","doi":"10.4103/NRR.NRR-D-24-00537","DOIUrl":"10.4103/NRR.NRR-D-24-00537","url":null,"abstract":"<p><p>Epilepsy, a common neurological disorder, is characterized by recurrent seizures that can lead to cognitive, psychological, and neurobiological consequences. The pathogenesis of epilepsy involves neuronal dysfunction at the molecular, cellular, and neural circuit levels. Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits. The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy. Therefore, this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies, including electroencephalography, magnetic resonance imaging, optogenetics, chemogenetics, deep brain stimulation, and brain-computer interfaces. Additionally, this review discusses these mechanisms from three perspectives: structural, synaptic, and transmitter circuits. The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures, interactions within the same structure, and the maintenance of homeostasis at the cellular, synaptic, and neurotransmitter levels. These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"455-465"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037322","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":"Fat mass and obesity-mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury.","authors":"Xiangrong Chen, Jinqing Lai, Zhe Wu, Jianlong Chen, Baoya Yang, Chunnuan Chen, Chenyu Ding","doi":"10.4103/NRR.NRR-D-23-01854","DOIUrl":"10.4103/NRR.NRR-D-23-01854","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00042/figure1/v/2025-05-05T160104Z/r/image-tiff The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury. The post-transcriptional modification of N 6 -methyladenosine is ubiquitous in the immune response of the central nervous system. The fat mass and obesity-related protein catalyzes the demethylation of N 6 -methyladenosine modifications on mRNA and is widely expressed in various tissues, participating in the regulation of multiple diseases' biological processes. However, the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear. In this study, we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model. After fat mass and obesity interference, BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b + /CD86 + cells and the secretion of pro-inflammatory cytokines. Fat mass and obesity-mediated N 6 -methyladenosine demethylation accelerated the degradation of ADAM17 mRNA, while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA. Therefore, down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia. These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N 6 -methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"730-741"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154638","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":"Zebrafish optic nerve regeneration involves resident and retinal oligodendrocytes.","authors":"Cristina Pérez-Montes, Rosalía Hernández-García, Jhoana Paola Jiménez-Cubides, Laura DeOliveira-Mello, Almudena Velasco, Rosario Arévalo, Marina García-Macia, Adrián Santos-Ledo","doi":"10.4103/NRR.NRR-D-24-00621","DOIUrl":"10.4103/NRR.NRR-D-24-00621","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00049/figure1/v/2025-05-05T160104Z/r/image-tiff The visual system of teleost fish grows continuously, which is a useful model for studying regeneration of the central nervous system. Glial cells are key for this process, but their contribution is still not well defined. We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6, 24, and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy. To understand the changes that these oligodendrocytes undergo during regeneration, we used Sox2 immunohistochemistry, a stem cell marker involved in oligodendrocyte differentiation. We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation. Before optic nerve crush, sox10:tagRFP oligodendrocytes are located in the retina, in the optic nerve head, and through all the entire optic nerve. Sox2-positive cells are present in the peripheral germinal zone, the mature retina, and the optic nerve. After optic nerve crush, sox10:tagRFP cells disappeared from the optic nerve crush zone, suggesting that they died, although they were not TUNEL positive. Concomitantly, the number of Sox2-positive cells increased around the crushed area, the optic nerve head, and the retina. Then, between 24 hours post-lesion and 14 days post-lesion, double sox10:tagRFP /Sox2-positive cells were detected in the retina, optic nerve head, and whole optic nerve, together with a proliferation response at 72 hours post-lesion. Our results confirm that a degenerating process may occur prior to regeneration. First, sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them, change their \"myelinating oligodendrocyte\" morphology to a \"nonmyelinating oligodendrocyte\" morphology, and die. Then, residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination. As new axons arise from the surviving retinal ganglion cells, new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide, nourish and myelinate them. Thus, oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"811-820"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059476","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":"Amyloid-β is NOT only the most promising target for Alzheimer's disease.","authors":"Beka Solomon, Milana Voronov-Goldman","doi":"10.4103/NRR.NRR-D-24-00829","DOIUrl":"10.4103/NRR.NRR-D-24-00829","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"681-682"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813719","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":"Metabolic reprogramming of astrocytes: Emerging roles of lactate.","authors":"Zeyu Liu, Yijian Guo, Ying Zhang, Yulei Gao, Bin Ning","doi":"10.4103/NRR.NRR-D-24-00776","DOIUrl":"10.4103/NRR.NRR-D-24-00776","url":null,"abstract":"<p><p>Lactate serves as a key energy metabolite in the central nervous system, facilitating essential brain functions, including energy supply, signaling, and epigenetic modulation. Moreover, it links epigenetic modifications with metabolic reprogramming. Nonetheless, the specific mechanisms and roles of this connection in astrocytes remain unclear. Therefore, this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system. The close relationship between epigenetic modifications and metabolic reprogramming was discussed. Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases. In the nervous system, lactate plays an essential role. However, its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation. The involvement of lactate in epigenetic modifications is currently a hot research topic, especially in lactylation modification, a key determinant in this process. Lactate also indirectly regulates various epigenetic modifications, such as N6-methyladenosine, acetylation, ubiquitination, and phosphorylation modifications, which are closely linked to several neurological disorders. In addition, exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"421-432"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838281","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":"Towards mechanism-based tau-targeted therapies.","authors":"Lidia Bakota, Roland Brandt","doi":"10.4103/NRR.NRR-D-24-01240","DOIUrl":"10.4103/NRR.NRR-D-24-01240","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"687-688"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009066","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":"Recent advances in immunotherapy targeting amyloid-beta and tauopathies in Alzheimer's disease.","authors":"Sha Sha, Lina Ren, Xiaona Xing, Wanshu Guo, Yan Wang, Ying Li, Yunpeng Cao, Le Qu","doi":"10.4103/NRR.NRR-D-24-00846","DOIUrl":"10.4103/NRR.NRR-D-24-00846","url":null,"abstract":"<p><p>Alzheimer's disease, a devastating neurodegenerative disorder, is characterized by progressive cognitive decline, primarily due to amyloid-beta protein deposition and tau protein phosphorylation. Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer's disease. Conventional drugs, such as donepezil, can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline. Currently, active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer's disease and other transgenic animal models, attracting considerable attention. However, the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab. This review first discusses the advancements in the pathogenesis of Alzheimer's disease and active and passive immunotherapies targeting amyloid-beta and tau proteins. Furthermore, it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects. Although some antibodies have shown promise in patients with mild Alzheimer's disease, substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer's disease.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"577-587"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066873","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":"Bromodomain-containing protein 4 knockdown promotes neuronal ferroptosis in a mouse model of subarachnoid hemorrhage.","authors":"Peng Lu, Fan Zhang, Lei Yang, Yijing He, Xi Kong, Kecheng Guo, Yuke Xie, Huangfan Xie, Bingqing Xie, Yong Jiang, Jianhua Peng","doi":"10.4103/NRR.NRR-D-24-00147","DOIUrl":"10.4103/NRR.NRR-D-24-00147","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00041/figure1/v/2025-05-05T160104Z/r/image-tiff Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage. Neuronal ferroptosis in particular plays an important role in early brain injury. Bromodomain-containing protein 4, a member of the bromo and extraterminal domain family of proteins, participated in multiple cell death pathways, but the mechanisms by which it regulates ferroptosis remain unclear. The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro . Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons, and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo . In addition, ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage. Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis. Using cleavage under targets and tagmentation analysis, we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro . Furthermore, treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074, a Raf-1 inhibitor, exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway. Moreover, targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage. Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage, and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"715-729"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893902","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}