Cellular model of neuronal atrophy induced by DYNC111 deficiency reveals protective roles of RAS-RAF-MEK signaling

Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein mal- function and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracallular signaling...

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Published in:蛋白质与细胞：英文版 2016 (9), p.638-650
Main Author: Zhi-Dong Liu Su Zhang Jian-Jin Hao Tao-Rong Xie Jian-Sheng Kang
Format: Article
Language:English
Subjects:
保护作用
信号显示
功能障碍
海马神经元
病理特征
神经退行性疾病
细胞模型
马达蛋白
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Summary:Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein mal- function and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracallular signaling pathways that can pro- tect against or delay this pathogenic process. Here, we show that the DYNClll 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 DYNClll 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 demon- strate protective roles of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic target for clinical intervention.
ISSN:1674-800X
1674-8018