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| 1 | The recommendations of Chinese Parkinson’s disease and movement disorder society consensus on therapeutic management of Parkinson’s disease显示文摘Background:Parkinson’s disease(PD)is a chronic,progressive and debilitating disease,which affects over 2.5 million people in China.PD is characterized clinically by resting tremor,muscular rigidity,bradykinesia and postural instability.As the disease progresses,additional complications can arise such as non-motor and neurobehavioral symptoms.Pharmacological treatment and surgical intervention for PD have been implemented in China.Until 10 years ago,there was lack of standardization for the management of PD in different regions and among different physicians,leading to different treatment levels in different regions and different physicians.Since then,the Chinese Parkinson’s Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China,in 2006,2009 and 2014,respectively.Correspondingly,the overall level of treatment for PD in China improved.Objectives:To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence,and to improve the treatment options available to physicians in the management of PD.Summary:A variety of treatment recommendations in the treatment guidelines have been proposed,including physical activity and disease-modifying medication,which should be initiated at the early-stage of the disease.The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs,to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications.Moreover,different treatment strategies should be considered at different stages of the disease.Importantly,treatment guidelines and personalized treatments should be valued equally.A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China. | Shengdi Chen Piu Chan Shenggang Sun Haibo Chen Baorong Zhang Weidong Le Chunfeng Liu Guoguang Peng Beisha Tang Lijuan Wang Yan Cheng Ming Shao Zhenguo Liu Zhenfu Wang Xiaochun Chen Mingwei Wang Xinhua Wan Huifang Shang Yiming Liu Pingyi Xu Jian Wang Tao Feng Xianwen Chen Xingyue Hu Anmu Xie Qin Xiao | 2016 | Translational Neurodegeneration2016，5，1： | 23 |
| 2 | Standardized Operational Protocol for Human Brain Banking in China显示文摘With the progress of society, there is an increasing need to tackle disorders of the central nervous system. Human brain tissue, unlike animal tissues, is an irreplaceable resource for the study of neurological diseases (1)Aimed at scientific research and education, the roles of human brain tissue repositories are to acquire brain tissue from donors, prepare, process, and preserve collected samples,provide tissue to specific eligible facilities, and determine the characteristics of each tissue sample. | Wenying Qiu Hanlin Zhang Aimin Bao Keqing Zhu Yue Huang Xiaoxin Yan Jing Zhang Chunjiu Zhong Yong Shen Jiangning Zhou Xiaoying Zheng Liwei Zhang Yousheng Shu Beisha Tang Zhenxin Zhang Gang Wang Ren Zhou Bing Sun Changlin Gong Shumin Duan Chao Ma | 2019 | Neuroscience Bulletin2019，35，2： | 6 |
| 3 | Clinical classification and gene mutation of Chinese probands with Charcot-Marie-Tooth disease Analysis of 57 cases显示文摘Charcot-Marie-Tooth(CMT) disease is the most common inherited peripheral neuropathic disorder.CMT is clinically and genetically heterogeneous.To date,27 genes associated with the disease have been cloned.The present study carried out clinical classification according to clinical,electrophysiological and pathological features,conducted inheritance classification according to inheritance patterns,and performed mutation analysis of 13 CMT disease genes(PMP22,CX32,HSPB1,MNF2,MPZ,HSPB8,GDAP1,NFL,EGR2,SIMPLE,RAB7,LMNA,MTMR2) in 57 Chinese probands with CMT.Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A;five cases of X-CMT1,one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTX1;four cases of AD-CMT2 were diagnosed as CMT2F;one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2;one case of AD-CMT2 was diagnosed as CMT2L;one case of AD-CMT2 was diagnosed as CMT2J;one case of AR-CMT1 was diagnosed as CMT4A.Among the 57 CMT probands,seven genotypes were determined among 34 patients,with a detection rate of 59.6%.The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection,and for efficient molecular diagnosis. | Ruxu Zhang Xiaobo Li Xiaohong Zi Shunxiang Huang Fufeng Zhang Kun Xia Qian Pan Beisha Tang | 2011 | Neural Regeneration Research2011，6，9： | 4 |
| 4 | Chaperone-mediated autophagy and neurodegeneration:connections,mechanisms,and therapeutic implications显示文摘Lysosomes degrade dysfunctional intracellular components via three pathways: macroautophagy, microautophagy, and chaperone-mediated autophagy(CMA). Unlike the other two, CMA degrades cytosolic proteins with a recognized KFERQ-like motif in lysosomes and is important for cellular homeostasis. CMA activity declines with age and is altered in neurodegenerative diseases. Its impairment leads to the accumulation of aggregated proteins, some of which may be directly tied to the pathogenic processes of neurodegenerative diseases. Its induction may accelerate the clearance of pathogenic proteins and promote cell survival, representing a potential therapeutic approach for the treatment of neurodegenerative diseases. In this review, we summarize the current findings on how CMA is involved in neurodegenerative diseases, especially in Parkinson's disease. | Xiaolei Liu Sihua Huang Xingqin Wang Beisha Tang Wenming Li Zixu Mao | 2015 | Neuroscience Bulletin2015，31，4： | 4 |
| 5 | The APOE ε2 allele may decrease the age at onset in patients with spinocerebellar ataxia type 3 or Machado-Joseph disease from the Chinese Han population显示文摘 | Huirong Peng Chunrong Wang Zhao Chen Zhanfang Sun Bin Jiao Kai Li Fengzhen Huang Xuan Hou Junling Wang Lu Shen Kun Xia Beisha Tang Hong Jiang | 2014 | Neurobiology of Aging2014，，9： | 1 |
| 6 | RNA interference blocking the apoptosis in HEK293 cells induced by overexpression of alpha-synuclein显示文摘BACKGROUND:Overexpression ofα-synuclein can induce cell apoptosis.RNA interference(RNAi) may block specific gene function and cause gene silencing. OBJECTIVE:To construct a specific and effective RNAi plasmid for theα-synuclein gene and investigate if RNAi can block apoptosis in HEK293 cells,induced by overexpression of wild-typeα-synuclein. DESIGN,TIME AND SETTING:A contrast experiment based on genetically engineered cytobiology was performed at the State Key Lab of Medical Genetics of China,Xiangya Medical College of Central South University,between October 2004 and October 2008. MATERIALS:HEK293 cells and pBSHH1 plasmid were provided by the State Key Lab of Medical Genetics of China;OligDNA sequence by Sagon Bioengineering Company,Shanghai; Lipofectamine 2000 by Invitrogen,USA;α-synuclein monoclonal antibody,Hoechst 33258,and MTT; by Sigma,USA;Horseradish peroxidase-coupled goat anti-rat IgG by KPL,USA;FACSan flow cytometry by BD,USA. METHODS:Four target sites were used to construct hairpin RNA pBSHH1 vectors-pSYNi-1, pSYNi-2,pSYNi-3 and pSYNi-4-which were cloned in the pBSHH1 plasmid.HEK293 cells were transfected using Lipofectamine 2000.In addition,a non-transfect group and a negative plasmid transfect group were established.The cultured HEK293 cells were processed as follows: transfection of blank plasmid(blank control group),transfection ofα-synuclein-pEGFP and RNAi negative vector(negative control group),and transfection ofα-synuclein-pEGFP and pSYNi-1 (transfection group).Cells in all groups were transfected with Lipofectamine 2000 for 48 hours. MAIN OUTCOME MEASURES:Expression ofα-synuclein mRNA and protein were detected by RT-PCR and Western blot.Cell morphology was observed under an inverted fluorescence microscope;cell viability was measured using MTT method;and cell apoptosis was determined with Annexin V-PE flow cytometry. RESULTS:α-synuclein mRNA and protein expressions were significantly decreased in the pSYNi-1 group when compared with the non-transfect and negative plasmid transfect groups(P<0.05).The expressions were partially decreased in the pSYNi-2 group,but there was no significant difference in the pSYNi-3 and pSYNi-4 groups.Hoechst staining indicated that cell nuclei were enlarged in the negative control group,coloring was not uniform,and chromatin was accumulated and appeared spot-like.The nucleus coloring was uniform in the transfection group compared to negative control group.Cell viability in the negative control group was significantly lower than blank control group with cell apoptosis being significantly increased(P<0.05).In comparison with negative control group, cell viability was significantly increased in the transfection group and cell apoptosis was significantly decreased(P<0.05). CONCLUSION:pSYNi-1 can inhibitα-synuclein gene expression and block apoptosis of HEK293 cells induced by overexpression of wild-typeα-synuclein. | Tao Chen Beisha Tang Xiaoping Liao Guoqiang Wen Xinxiang Yan Jifeng Guo Yuhu Zhang Feng Ouyang Zhigang Long Li Cao Jing Li | 2009 | Neural Regeneration Research2009，4，7： | 1 |
| 7 | A novel transgenic mouse model of Chinese CharcotMarie-Tooth disease type 2L显示文摘We previously found that the K141N mutation in heat shock protein B8(HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family.The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene,and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L,and consequently be suitable for use in studies of disease pathogenesis.Transgenic mice overexpressing K141NHSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system.PCR and western blot analysis confirmed integration of the K141NHSPB8 gene and widespread expression in tissues of the transgenic mice.The K141NHSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination,but no obvious sensory disturbance at 6 months of age by behavioral assessment.Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased,but motor nerve conduction velocity remained normal at 6 months of age.Pathological analysis of the sciatic nerve showed reduced myelinated fiber density,notable axonal edema and vacuolar degeneration in K141NHSPB8 transgenic mice,suggesting axonal involvement in the peripheral nerve damage in these animals.These findings indicate that the K141NHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease. | Ruxu Zhang Fufeng Zhang Xiaobo Li Shunxiang Huang Xiaohong Zi Ting Liu Sanmei Liu Xuning Li Kun Xia Qian Pan Beisha Tang | 2014 | Neural Regeneration Research2014，9，4： | 1 |
| 8 | Recommendations for the diagnosis and treatment of paroxysmal kinesigemc dyskinesia: an expert consensus in China显示文摘Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes.Paroxysmal kinesigenic dyskinesia(PKD)is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology.Clinically,PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action.The major cause of primary PKD is genetic abnormalities,and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance.The proline-rich transmembrane protein 2(PRRT2)was the first identified causative gene of PKD,accounting for the majority of PKD cases worldwide.An increasing number of studies has revealed the clinical and genetic characteristics,as well as the underlying mechanisms of PKD.By seeking the views of domestic experts,we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD.In this consensus,we review the clinical manifestations,etiology,clinical diagnostic criteria and therapeutic recommendations for PKD,and results of genetic analyses in PKD patients performed in domestic hospitals. | Li Cao Xiaojun Huang Ning Wang Zhiying Wu Cheng Zhang Weihong Gu Shuyan Cong Jianhua Ma Ling Wei Yanchun Deng Qi Fang Qi Niu Jin Wang Zhaoxia Wang You Yin Jinyong Tian Shufen Tian Hongyan Bi Hong Jiang Xiaorong Liu Yang Lu Meizhen Sun Jianjun Wu Erhe Xu Tao Chen Tao Chen Xu Chen Wei Li Shujian Li Qinghua Li Xiaonan Song Ying Tang Ping Yang Yun Yang Min Zhang Xiong Zhang Yuhu Zhang Ruxu Zhang Yi Ouyang Jintai Yu Quanzhong Hu Qing Ke Yuanrong Yao Zhe Zhao Xiuhe Zhao Guohua Zhao Furu Liang Nan Cheng Jianhong Han Rong Peng Shengdi Chen Beisha Tang | 2021 | Translational Neurodegeneration2021，10，1： | 1 |
| 9 | Prenatal diagnosis of spinocerebellar ataxia type 3/Machado-Joseph disease in China's Mainland A case report显示文摘Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive, currently untreatable and ultimately fatal ataxic disorder that belongs to the group of neurological disorders known as CAG-repeat or polyglutamine diseases. Here, we present the first prenatal diagnosis of SCA3/MJD in China's Mainland in a woman who was known to carry an expanded CAG-trinucleotide repeat in the MJD1 gene. After evaluating motivation and psychological tolerance of the couple, amniocentesis was performed after 14 weeks of gestation. Polymerase chain reactions followed by T-vector cloning and direct sequencing were employed to evaluate the CAG-repeat number of the fetal MJD1 gene. We identified a truncated CAG expansion of 78 repeats in the MJD1 gene of the fetus compared with 81 repeats in his mother. | Lifang Lei Junling Wang Shen Zhang Hong Jiang Lu Shen Qian Xu Xinxiang Yan Yi Yuan Qian Pan Kun Xia Beisha Tang | 2011 | Neural Regeneration Research2011，6，26： | 1 |
| 10 | Efficacy and safety of light therapy for Parkinson disease显示文摘To the Editor:Parkinson disease(PD)is the second most common neurodegenerative disorder associated with significant disability and negative impact on quality of life(QoL),affecting 2%to 3%of the population≥65 years of age.^([1])Although the disorder is defined by motor features including asymmetric tremor,bradykinesia,and rigidity,various non-motor features are typically seen,including cognitive impairment,depression,sensory symptoms,autonomic dysfunction,and sleep disturbances.Due to the complexity,PD is challenging to treat.There are currently no effective treatments to prevent or halt the progression of PD. | Yanghong Li Xiaoxia Zhou Xinyin Wu Beisha Tang | 2022 | Chinese Medical Journal2022，，7： | 1 |
| 11 | Performance Comparison of Computational Methods for the Prediction of the Function and Pathogenicity of Non-coding Variants显示文摘Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects.Hence,an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences.However,it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods.To solve this issue,we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets:(1)rare germline variants from clinical relevant sequence variants(ClinVar),(2)rare somatic variants from Catalogue Of Somatic Mutations In Cancer(COSMIC),(3)common regulatory variants from curated expression quantitative trait locus(eQTL)data,and(4)disease-associated common variants from curated genomewide association studies(GWAS).All 24 tested methods performed differently under various conditions,indicating varying strengths and weaknesses under different scenarios.Importantly,the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve(AUROC)of 0.4481–0.8033 and poor for rare somatic variants from COSMIC(AUROC=0.4984–0.7131),common regulatory variants from curated eQTL data(AUROC=0.4837–0.6472),and disease-associated common variants from curated GWAS(AUROC=0.4766–0.5188).We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder,and found that the combined annotation-dependent depletion(CADD)and context-dependent tolerance score(CDTS)methods showed better performance.Summarily,we assessed the performance of 24 computational methods under diverse scenarios,providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants. | Zheng Wang Guihu Zhao Bin Li Zhenghuan Fang Qian Chen Xiaomeng Wang Tengfei Luo Yijing Wang Qiao Zhou Kuokuo Li Lu Xia Yi Zhang Xun Zhou Hongxu Pan Yuwen Zhao Yige Wang Lin Wang Jifeng Guo Beisha Tang Kun Xia Jinchen Li | 2023 | Genomics, Proteomics & Bioinformatics2023，21，3： | 0 |
| 12 | Functional characterization of novel NPRL3 mutations identified in three families with focal epilepsy显示文摘Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup C and 6,706-bp genomic DNA(g DNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing(WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of m TOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced m TOR signaling in cultured cells, possibly due to impaired inhibition of m TORC1 by GATOR1. Knockdown of nprl3 in Drosophila resulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3 mutations lead to epilepsy. | Shiyue Du Sheng Zeng Li Song Hongying Ma Rui Chen Junyu Luo Xu Wang Tingbin Ma Xuan Xu Hao Sun Ping Yi Jifeng Guo Yaling Huang Mugen Liu Tao Wang Wei-Ping Liao Luoying Zhang Jing Yu Liu Beisha Tang | 2023 | Science China(Life Sciences)2023，66，9： | 0 |
| 13 | Rare TBK1 variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort显示文摘Background:The TANK-Binding Kinase 1(TBK1)gene has recently been identified as the third or fourth most frequent cause of frontotemporal dementia(FTD)and amyotrophic lateral sclerosis(ALS).The aim of this study was to assess the genetic contribution of TBK1 in a Chinese cohort.Methods:A total of 270 cases with ALS,FTD,or their combination were recruited into this study.All the coding exons of TBK1 and intron-exon boundaries were sequenced using Sanger sequencing.The frequency of TBK1 variants and the correlation with clinical phenotypes were analyzed.Results:A novel mutation(c.1959_1960insGT,p.E653fs)was identified in a sporadic case with semantic dementia,secondarily developing ALS.Another novel variant(c.2063_2064delTT,p.L688Rfs*14)was found in an ALS-FTD family.Totally,the TBK1 variants could only account for 0.7% of cases.Conclusions:This study enlarges the genetic and phenotypic spectrum of TBK1 mutation in a Chinese cohort.Our data indicates that TBK1 mutation is not a common cause for ALS and FTD in Chinese patients. | Bin Jiao Qiying Sun Zhenhua Yuan Junling Wang Lin Zhou Xinxiang Yan Beisha Tang Lu Shen | 2018 | Translational Neurodegeneration2018，7，1： | 0 |
| 14 | Clinical and genetic analysis of two Chinese families with benign familial neonatal convulsions显示文摘Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant inherited epilepsy syndrome. Two voltage-gated potassium channel genes, KCNQ2 and KCNQ3, have been identified as the genes responsible for BFNC. Here we report two Chinese families with clinical histories of typical BFNC. Using six microsatellite markers, two located at KCNQ2 locus and four at KCNQ3 locus, linkage analysis was performed in the two families, which excluded the linkage of BFNC to KCNQ3, but could not exclude the linkage to KCNQ2. Direct DNA sequencing of the KCNQ2 gene in the two families was performed, and two formerly unknown polymorphisms were identified, but no KCNQ2 mutation was found in the two families. Our study suggests the genetic heterogeneity in Chinese families with BFNC and proves the existence of a new gene locus for BFNC. | LI Haiyan TANG Beisha XIA Kun CAO Guifang SHEN Lu JIANG Hong PAN Qian SONG Yanmin CAI Fang | 2005 | Progress in Natural Science:Materials International2005，15，8： | 0 |
| 15 | Association of variants in the KIF1A gene with amyotrophic lateral sclerosis显示文摘Background:Amyotrophic lateral sclerosis(ALS)is a devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal cord.As in many other neurodegenerative disorders,the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal transport.Notably,sen-sory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2(HSAN2)and spastic paraplegia 30(SPG30)share several causative genes with ALS,as well as having common clinical phenotypes.KIF1A encodes a kinesin 3 motor that transports presynaptic vesicle precursors(SVPs)and dense core vesicles and has been reported as a causative gene for HSAN2 and SPG30.Methods:Here,we analyzed whole-exome sequencing data from 941 patients with ALS to investigate the genetic association of KIF1A with ALS.Results:We identified rare damage variants(RDVs)in the KIF1A gene associated with ALS and delineated the clini-cal characteristics of ALS patients with KIF1A RDVs.Clinically,these patients tended to exhibit sensory disturbance.Interestingly,the majority of these variants are located at the C-terminal cargo-binding region of the KIF1A protein.Functional examination revealed that the ALS-associated KIF1A variants located in the C-terminal region preferentially enhanced the binding of SVPs containing RAB3A,VAMP2,and synaptophysin.Expression of several disease-related KIF1A mutants in cultured mouse cortical neurons led to enhanced colocalization of RAB3A or VAMP2 with the KIF1A motor.Conclusions:Our study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS,indicating KIF1A as an important player in the oligogenic scenario of ALS. | Panlin Liao Yanchun Yuan Zhen Liu Xiaorong Hou Wanzhen Li Jin Wen Kexuan Zhang Bin Jiao Lu Shen Hong Jiang Jifeng Guo Beisha Tang Zhuohua Zhang Zhonghua Hu Junling Wang | 2022 | Translational Neurodegeneration2022，11，1： | 0 |
| 16 | Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients显示文摘We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an 'onion-like' structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and 'mouse-nibbled'-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced. | Xiaobo Li Xiaohong Zi Lin Li Yajing Zhan Shunxiang Huang Jin Li Xuning Li Xigui Li Zhengmao Hu Kun Xia Beisha Tang Ruxu Zhang | 2012 | Neural Regeneration Research2012，7，32： | 0 |
| 17 | The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways显示文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction. | Sen Zeng Honglan Yang Binghao Wang Yongzhi Xie Ke Xu Lei Liu Wanqian Cao Xionghao Liu Beisha Tang Mujun Liu Ruxu Zhang | 2024 | Neural Regeneration Research2024，19，1： | 0 |
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