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Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

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Neural Regeneration Research 2024年第4期19卷 881-886页

作者： Fan Bu Jia-Wei Min Md Abdur Razzaque Ahmad El Hamamy Anthony Patrizz Li Qi Akihiko Urayama Jun Li department of neurology University of Texas Health Science Center department of neurology&Psychology The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain *** is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following *** evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced *** studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke ***,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic *** found that as mice aged,Rac1 expression declined in the *** overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–*** was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by *** a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial ***,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after *** work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

关键词： aging angiogenesis brain-derived neurotrophic factor(BDNF) cerebral ischemia cognitive recovery neurite Pak1 Rac1 sensorimotor recovery

Multiple sclerosis drug repurposing for neuroregeneration

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Neural Regeneration Research 2024年第3期19卷 507-508页

作者： Peter Göttle Michael Dietrich Patrick Küry department of neurology Medical FacultyHeinrich-Heine UniversityDüsseldorfGermany

Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turning progressive over time with neurodegenerative processes taking over(Amin and Hersh,2023).Of note,beyond relapse-associated worsening early in disease progression independent of relapse activity may arise independently of relapse activity and can occur in all ***-mediated damage of myelin sheaths and the subsequent loss of mature oligodendrocytes are resulting in impaired axonal integrity,neurodegeneration and accounts for irreversible neuronal damage(Kuhlmann et al.,2023).The current landscape of available disease-modifying therapies comprises mainly immunomodulatory drugs that effectively diminish relapses and slow down progression at the onset form of the disease,namely relapsing MS(RMS).In this regard,a number of drugs have been approved as disease-modifying therapies for MS by US Food and Drug Administration and European Medicines Agencies(Box 1).

关键词： drugs impaired irreversible

Rbm8a regulates neurogenesis and reduces Alzheimer's disease-associated pathology in the dentate gyrus of 5×FAD mice

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Neural Regeneration Research 2024年第4期19卷 863-871页

作者： Chenlu Zhu Xiao Ren Chen Liu Yawei Liu Yonggang Wang department of neurology Lanzhou University Second Hospital department of neurology The First Affiliated Hospital of Nanchang University department of neurology Xiaogan City Central Hospital Health Service department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China Headache Center Department of NeurologyBeijing Tiantan HospitalCapital Medical University

Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal *** in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s *** evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy *** study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s ***,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this *** Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD *** sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein *** conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.

关键词： Adora2a Alzheimer’s disease astrocyte cAMP signaling pathway dentate gyrus dystrophic neurites microglia neurogenesis plaque Rbm8a

CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： Yan Shi Chunyan Cao Yiheng Zeng Yuanliang Ding Long Chen Fuze Zheng Xuejiao Chen Fanggui Zhou Xiefeng Yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang Yang department of neurology and Institute of neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China department of neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China department of neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China department of neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China department of neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan department of neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Institute of medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with ***,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/***,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal *** CGG repeat expansions range from 161 to 669 repeat *** of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle *** one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance *** biopsies from three patients show a myopathic pattern and rimmed *** of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to *** study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

International standard of Traditional Chinese Medicine Techniques: Traditional Chinese Medicine guidelines for acute primary headache(2022)

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Journal of Traditional Chinese Medicine 2024年第4期44卷 839-850页

作者： YAO Yuning CAO Kegang ZHANG Genming LIU Jianping CHEN Wei CAO Junling YANG Wenming YAN Yongmei GENG Chang JU Yi ZHAO Dexi QU Miao LI Xiaoli SUN Li HAN Zhenyun HE Liyun CUI Fangyuan FU Caihong ZHOU Bo LIAO Shuqin department of neurology Dongzhimen Hospital of Beijing University of Chinese MedicineBeijing 100007China Centre for Evidence-Based Chinese Medicine Beijing University of Chinese MedicineBeijing 100029Chin Encephalopathy center First Affiliated Hospital of Anhui University of Chinese MedicineHefei 230031China department of neurology Affiliated Hospital of Shaanxi University of Chinese MedicineXi'an 710077China department of neurology Beijing Changping District Hospital of Traditional Chinese MedicineBeijing 102299China neurology center Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China department of neurology Affiliated Hospital of Changchun University of Chinese MedicineChangchun 130021China department of neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin department of neurology Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China department of Geriatrics Jilin Academy of Traditional Chinese MedicineChangchun 130012China department of neurology Shenzhen Hospital of Beijing University of Chinese MedicineShenzhen 518172China Institute of Basic Research in Clinical Medicine China Academy Of Chinese Medical SciencesBeijing 100700Chin department of Rehabilitation Shunyi HospitalBeijing Traditional Chinese Medicine HospitalBeijng 101300China department of neurology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China

OBJECTIVE:To summarize the evidence from Traditional Chinese Medicine(TCM)practice in the treatment of acute primary headache and provide clinical practice ***:The guidelines were developed in accordance with the World Health Organization guideline development *** the establishment of steering committee,panel and the registration and protocol formulation,the evidence on TCM for acute primary headache from published guidelines,clinical evidence,and expert experience and consensus were *** grading of recommendations assessment,development and evaluation method was used to grade the evidence and make the ***:Based on the available evidence,the guidelines recommended three TCM herbal decoctions,six Chinese patent medicines,and two kinds of external application of Chinese herbal *** recommendations based on the expert experience and consensus were also included in the ***:TCM diagnosis and treatment of decoction,Chinese patent medicine and external application for treating acute primary headache were *** hope these guidelines will be helpful in standardize the TCM acute treatment of primary headache.

关键词： medicine,Chinese traditional acute primary headache practice guideline

The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu medical College of Nanchang University department of neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory ***,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the *** disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

Alterations in expression and localization of POMGNT1 in the APP/PS1 mouse model of Alzheimer’s disease

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Genes & Diseases 2024年第5期11卷 55-58页

作者： Hanxiao Jiang Yuxue Feng Xia Hao Guiqiong He Xiaofeng Li department of neurology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 401336China Chongqing Key Laboratory of Neurobiology Chongqing Medical UniversityChongqing 400016China department of Anatomy Chongqing Medical UniversityChongqing 400016China department of neurology The Fifth People’s Hospital of ChongqingChongqing 400062China

Alzheimer’s disease(AD)is a complex and progressive neurodegenerative disorder that causes dementia in the aging *** of the characteristic pathologic hallmarks of AD is the senile plaques,composed of the accumulation of *** b-amyloid results from the cleavage of transmembrane b-amyloid precursor protein(APP)by b-secretases and g-secretases,sequentially.O-mannosylation was found essential for the normal function of APP in Saccharomyces cerevisiae.1 Protein Olinked mannose b1,2-N-acetyl-glucosaminyltransferase 1(POMGNT1)is a glycosyltransferase crucial for the elongation of O-mannosyl glycans and catalyzes the transfer of Nacetylglucosamine from uridine 50-diphosphate-N-acetylglucosamine to O-mannose of glycoproteins.

关键词： APP/PS1 Alzheimer amyloid

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li Xiang Cao Xinya Gu Mengqi Dong Lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang Yun Xu department of neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China department of neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China department of neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China department of neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of neurology Nanjing210008China Nanjing neurology medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal *** inflammation is associated with the occurrence and development of ***,the mechanisms underlying the formation of the abnormal vascular network remain ***-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in *** found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and *** summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

关键词： Moyamoya disease Vascular endothelial cells GM-CSF VEGF

Pathological mechanisms of amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第5期19卷 1036-1044页

作者： Yushu Hu Wenzhi Chen Caihui Wei Shishi Jiang Shu Li Xinxin Wang Renshi Xu department of Clinical Medicine Nanchang UniversityNanchangJiangxi ProvinceChina department of neurology Jiangxi Provincial People’s HospitalNanchangJiangxi ProvinceChina department of neurology The First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of ***,the journey to understanding or treating amyotrophic lateral sclerosis is still a long *** to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic *** progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral ***,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral *** addition,we discuss current emerging strategies for the treatment of amyotrophic lateral *** the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

关键词： amyotrophic lateral sclerosis cellular pathways disease mechanisms motor neuron neurodegenerative disease