TDP-43参与肌萎缩侧索硬化症的病理机制研究进展
| 作者: |
1黄茂鑫,
1廉宏想,
2王俊岭
1 中南大学湘雅医学院，长沙 410078 2 中南大学湘雅医院神经内科，长沙 410008 |
| 通讯: |
王俊岭
Email: wjling8002@126.com |
| DOI: | 10.3978/j.issn.2095-6959.2021.07.032 |
| 基金: | 国家重点研发计划(2018YFC1312003)；国家自然科学基金(81671120，81300981)；中南大学湘雅医院临床科研基金(2015105)。 |
摘要
肌萎缩侧索硬化症(amyotrophic lateral sclerosis，ALS)是以选择性上、下运动神经元损害为特征的慢性进行性神经系统变性疾病，其发病机制尚不明确。TDP-43(transactive response DNA-binding protein-43)在细胞质中形成包涵体是ALS的特征性病理标志之一。病理性TDP-43通过影响细胞内多种生理过程介导了神经退变的发生，如TDP-43可损害线粒体功能，引发内质网应激(endoplasmic reticulum stress，ER stress)，TDP-43的病理性聚集与应激颗粒(stress granule，SG)有密切关系，TDP-43可与细胞内降解途径相互作用产生细胞保护或细胞毒性效应等。
关键词：
肌萎缩侧索硬化症；TDP-43；发病机制
Research progress in the involvement of TDP-43 in the pathogenesis of amyotrophic lateral sclerosis
CorrespondingAuthor: WANG Junling Email: wjling8002@126.com
DOI: 10.3978/j.issn.2095-6959.2021.07.032
Foundation: This work was supported by the National Key Research & Development Program of China (2018YFC1312003), National Natural Science Foundation of China (81671120, 81300981) and Clinical Research Foundation of Xiangya Hospital, Central South University (2015105), China.
Abstract
Amyotrophic lateral sclerosis (ALS) is a chronic and progressive neurodegenerative disease characterized with selective loss of upper and lower motor neurons, and the pathogenesis of it still remains elusive. One of the pathologic hallmarks of ALS is the presence of transactive response DNA-binding protein-43 (TDP-43)-containing cytoplasmic inclusions. Pathologic TDP-43 causes neurodegeneration via affecting various cellular physiological processes, including impairing mitochondrial function, triggering endoplasmic reticulum stress, being closely related to stress granule formation, and interacting with intracellular degradation pathways to exert protective or cytotoxic effects and so on.
Keywords：
amyotrophic lateral sclerosis; TDP-43; pathogenesis