期刊
PROTEIN & CELL
卷 7, 期 9, 页码 638-650出版社
OXFORD UNIV PRESS
DOI: 10.1007/s13238-016-0301-6
关键词
RAS-RAF-MEK pathway; atrophy; dynein intermediate chain; mitochondria; hippocampal neuron; autophagy
类别
资金
- National Natural Science Foundation of China [31171369]
- National Basic Research Program (973 Program) [2011CB910903, 2010CB912001]
- Chinese Academy of Sciences (Hundred Talents Program) [2009OHTP10]
Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein malfunction and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracellular signaling pathways that can protect against or delay this pathogenic process. Here, we show that the DYNC1I1 deficiency, a neuron-specific dynein intermediate chain, causes neuronal atrophy in primary hippocampal neurons. With this cellular model, we are able to find that activation of RAS-RAF-MEK signaling protects against neuronal atrophy induced by DYNC1I1 deficiency, which relies on MEK-dependent autophagy in neuron. Moreover, we further reveal that BRAF also protects against neuronal atrophy induced by mitochondrial impairment. These findings demonstrate protective roles of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic target for clinical intervention.
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