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Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling
Protein & Cell ; (12): 638-650, 2016.
Article in English | WPRIM | ID: wpr-757390
ABSTRACT
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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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Cell Line / Mice, Knockout / Ras Proteins / Neurodegenerative Diseases / MAP Kinase Kinase Kinases / MAP Kinase Signaling System / Proto-Oncogene Proteins B-raf / Cytoplasmic Dyneins / Genetics Type of study: Prognostic study Limits: Animals Language: English Journal: Protein & Cell Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Cell Line / Mice, Knockout / Ras Proteins / Neurodegenerative Diseases / MAP Kinase Kinase Kinases / MAP Kinase Signaling System / Proto-Oncogene Proteins B-raf / Cytoplasmic Dyneins / Genetics Type of study: Prognostic study Limits: Animals Language: English Journal: Protein & Cell Year: 2016 Type: Article