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Nuclear TAR DNA-binding protein 43 A new target for amyotrophic lateral sclerosis treatment
Zheng, Mei1; Shi, Yujie2; Fan, Dongsheng1
关键词Neural Regeneration Neurodegenerative Disease Amyotrophic Lateral Sclerosis Tar Dna-binding Protein 43 Cortex Motor Neurons Oxidative Stress Sodium Malonate Neuroprotection Grants-supported Paper Neurodegeneration
刊名NEURAL REGENERATION RESEARCH
2013-12-01
DOI10.3969/j.issn.1673-5374.2013.35.003
8期:35页:3284-3295
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Neurosciences
研究领域[WOS]Cell Biology ; Neurosciences & Neurology
关键词[WOS]FRONTOTEMPORAL LOBAR DEGENERATION ; TDP-43 TRANSGENIC MICE ; OXIDATIVE STRESS ; MOTOR-NEURONS ; DROSOPHILA MODEL ; PATHOLOGICAL MODIFICATIONS ; ENDOGENOUS TDP-43 ; RNA TARGETS ; SPINAL-CORD ; IN-VIVO
英文摘要

Abnormal TAR DNA-binding protein 43 (TDP-43) inclusion bodies can be detected in the degenerative neurons of amyotrophic lateral sclerosis. In this study, we induced chronic oxidative stress injury by applying malonate to cultured mouse cortical motor neurons. In the later stages of the malonate insult, TDP-43 expression reduced in the nuclei and transferred to the cytoplasm. This was accompanied by neuronal death, mimicking the pathological changes in TDP-43 that are seen in patients with amyotrophic lateral sclerosis. Interestingly, in the early stages of the response to malonate treatment, nuclear TDP-43 expression increased, and neurons remained relatively intact, without inclusion bodies or fragmentation. Therefore, we hypothesized that the increase of nuclear TDP-43 expression might be a pro-survival factor against oxidative stress injury. This hypothesis was confirmed by an in vitro transgenic experiment, in which overexpression of wild type mouse TDP-43 in cultured cortical motor neurons significantly reduced malonate-induced neuronal death. Our findings suggest that the loss of function of TDP-43 is an important cause of neuronal degeneration, and upregulation of nuclear TDP-43 expression might be neuroprotective in amyotrophic lateral sclerosis.

语种英语
WOS记录号WOS:000329336500003
项目编号81030019 ; 81200969 ; 73526-01
资助机构State Key Program of the Natural Science Foundation of China ; National Science Foundation for Young Scholars of China ; Peking University Third Hospital Scientific Research Foundation for Returned Scholars
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50792
专题北京大学第三临床医学院_神经内科
北京大学药学院_化学生物学系
作者单位1.Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
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GB/T 7714
Zheng, Mei,Shi, Yujie,Fan, Dongsheng. Nuclear TAR DNA-binding protein 43 A new target for amyotrophic lateral sclerosis treatment[J]. NEURAL REGENERATION RESEARCH,2013,8(35):3284-3295.
APA Zheng, Mei,Shi, Yujie,&Fan, Dongsheng.(2013).Nuclear TAR DNA-binding protein 43 A new target for amyotrophic lateral sclerosis treatment.NEURAL REGENERATION RESEARCH,8(35),3284-3295.
MLA Zheng, Mei,et al."Nuclear TAR DNA-binding protein 43 A new target for amyotrophic lateral sclerosis treatment".NEURAL REGENERATION RESEARCH 8.35(2013):3284-3295.
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