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 En
| WPRIM
| ID: wpr-757390
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Pathology
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Cell Line
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Mice, Knockout
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Ras Proteins
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Neurodegenerative Diseases
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MAP Kinase Kinase Kinases
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MAP Kinase Signaling System
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Proto-Oncogene Proteins B-raf
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Cytoplasmic Dyneins
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Genetics
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Protein & Cell
Year:
2016
Type:
Article