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.
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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