Neural Regeneration Research最新文献

{"title":"Novel genes involved in vascular dysfunction of the middle temporal gyrus in Alzheimer's disease: transcriptomics combined with machine learning analysis.","authors":"Meiling Wang, Aojie He, Yubing Kang, Zhaojun Wang, Yahui He, Kahleong Lim, Chengwu Zhang, Li Lu","doi":"10.4103/NRR.NRR-D-23-02004","DOIUrl":"10.4103/NRR.NRR-D-23-02004","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202512000-00030/figure1/v/2025-01-31T122243Z/r/image-tiff Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease. The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease. Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discovery of novel targets for intervention. We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls, revealing obvious changes in vascular function. CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients, with altered intercellular communication of endothelial cells and pericytes being the most prominent. Differentially expressed genes were also identified. Using the CellChat results, AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor (VEGF)A-VEGF receptor (VEGFR) 2 pathway. AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity. Two subtypes of middle temporal gyrus cells showed significant alteration in AD: endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4 (ERBB4 high ) and pericytes with high expression of angiopoietin-like 4 (ANGPTL4 high ). Finally, combining bulk RNA sequencing data and two machine learning algorithms (least absolute shrinkage and selection operator and random forest), four characteristic Alzheimer's disease feature genes were identified: somatostatin ( SST ), protein tyrosine phosphatase non-receptor type 3 ( PTPN3 ), glutinase ( GL3 ), and tropomyosin 3 ( PTM3 ). These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway. Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus. In conclusion, this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease. These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3620-3634"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inspires effective alternatives to backpropagation: predictive coding helps understand and build learning.","authors":"Zhenghua Xu, Miao Yu, Yuhang Song","doi":"10.4103/NRR.NRR-D-24-00629","DOIUrl":"10.4103/NRR.NRR-D-24-00629","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"20 11","pages":"3215-3216"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misfolded amyloid-beta conformational variants (strains) as drivers of Alzheimer's disease neuropathology.","authors":"Salvatore Saieva, Rodrigo Morales","doi":"10.4103/NRR.NRR-D-24-00699","DOIUrl":"10.4103/NRR.NRR-D-24-00699","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"20 11","pages":"3219-3220"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system.","authors":"Marta García-Juan, Mario Villa, Irene Benito-Cuesta, Lara Ordóñez-Gutiérrez, Francisco Wandosell","doi":"10.4103/NRR.NRR-D-24-00733","DOIUrl":"10.4103/NRR.NRR-D-24-00733","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"20 11","pages":"3209-3210"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretome of polarized macrophages: potential for targeting inflammatory dynamics in spinal cord injury.","authors":"Andreia Monteiro, Susana Monteiro, Nuno A Silva","doi":"10.4103/NRR.NRR-D-24-00752","DOIUrl":"10.4103/NRR.NRR-D-24-00752","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"20 11","pages":"3231-3232"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury.","authors":"Ziwei Fan, Mengxian Jia, Jian Zhou, Zhoule Zhu, Yumin Wu, Xiaowu Lin, Yiming Qian, Jiashu Lian, Xin Hua, Jianhong Dong, Zheyu Fang, Yuqing Liu, Sibing Chen, Xiumin Xue, Juanqing Yue, Minyu Zhu, Ying Wang, Zhihui Huang, Honglin Teng","doi":"10.4103/NRR.NRR-D-23-01256","DOIUrl":"10.4103/NRR.NRR-D-23-01256","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202511000-00031/figure1/v/2024-12-20T164640Z/r/image-tiff The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro . Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3287-3301"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway.","authors":"Jiayi Wang, Mengke Zhao, Dong Fu, Meina Wang, Chao Han, Zhongyue Lv, Liang Wang, Jing Liu","doi":"10.4103/NRR.NRR-D-23-01144","DOIUrl":"10.4103/NRR.NRR-D-23-01144","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202511000-00028/figure1/v/2024-12-20T164640Z/r/image-tiff Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3245-3258"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury.","authors":"Xiaoling Zhong, Wenjiao Tai, Meng-Lu Liu, Shuaipeng Ma, Tianjin Shen, Yuhua Zou, Chun-Li Zhang","doi":"10.4103/NRR.NRR-D-24-00113","DOIUrl":"10.4103/NRR.NRR-D-24-00113","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202511000-00027/figure1/v/2024-12-20T164640Z/r/image-tiff The mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults. Whether targeting this pathway is beneficial to brain injury remains unclear. In this study, we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis, tauopathy, lesion size, and behavioral deficits. Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain. Mechanistically, the Citron homology domain acted as a dominant-negative mutant, impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway. These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3233-3244"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging.","authors":"Holly Flyger, Samantha J Holdsworth, Alistair J Gunn, Laura Bennet, Hamid Abbasi","doi":"10.4103/NRR.NRR-D-24-00970","DOIUrl":"10.4103/NRR.NRR-D-24-00970","url":null,"abstract":"<p><p>Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in ~ 1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability. Detailed assessment is important to help identify high-risk infants, to help families, and to support appropriate interventions. A wide range of monitoring tools is available to assess changes over time, including urine and blood biomarkers, neurological examination, and electroencephalography. At present, magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy. This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries, with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction, particularly for infants treated with therapeutic hypothermia. A comprehensive literature search, from 2016 to 2024, identified 20 pertinent articles. This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear, overall, it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy. Many challenges limit the timing consistency, particularly the need for intensive care and clinical monitoring. Conversely, although most reports examined the prognostic value of scans taken between 4 and 10 days after birth, there is evidence from small numbers of cases that, at times, brain injury may continue to evolve for weeks after birth. This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3144-3150"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteostasis failure: at the intersection between aging and Alzheimer's disease.","authors":"Natalia Poblete, Claudio Hetz","doi":"10.4103/NRR.NRR-D-24-00658","DOIUrl":"10.4103/NRR.NRR-D-24-00658","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"20 11","pages":"3221-3222"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}