蛋白质与细胞：英文版, 2016 (9), p.638-650
2016
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- Autor(en) / Beteiligte
- Titel
- Cellular model of neuronal atrophy induced by DYNC111 deficiency reveals protective roles of RAS-RAF-MEK signaling
- Ist Teil von
- 蛋白质与细胞：英文版, 2016 (9), p.638-650
- Erscheinungsjahr
- 2016
- Quelle
- EZB Electronic Journals Library
- Beschreibungen/Notizen
- 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.