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学科主题: 临床医学
题名:
Nuclear TAR DNA-binding protein 43 A new target for amyotrophic lateral sclerosis treatment
作者: 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
发表日期: 2013-12-01
DOI: 10.3969/j.issn.1673-5374.2013.35.003
卷: 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
所属项目编号: 81030019 ; 81200969 ; 73526-01
项目资助者: 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
WOS记录号: WOS:000329336500003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50792
Appears in Collections:北京大学第三临床医学院_神经内科_期刊论文

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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

Recommended Citation:
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.
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