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Genetic suppression of collapsin response mediator protein 2 phosphorylation improves outcome in methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinson’s model mice
Author(s) -
Togashi Kentaro,
Hasegawa Masaya,
Nagai Jun,
Tonouchi Aine,
Masukawa Daiki,
Hensley Kenneth,
Goshima Yoshio,
Ohshima Toshio
Publication year - 2019
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12651
Subject(s) - biology , mediator , phosphorylation , outcome (game theory) , microbiology and biotechnology , neuroscience , mathematics , mathematical economics
Abstract Parkinson's disease (PD) is a common neurodegenerative disorder characterized by slow and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Levodopa ( l ‐Dopa), the current main treatment for PD, supplies dopamine, but it does not prevent neurodegeneration. There is thus no promising remedy for PD. Recent in vitro study showed the increase in the phosphorylation levels of Collapsin Response Mediator Protein 2 (CRMP2) is involved in dopaminergic axon degeneration. In the present study, we report elevation of CRMP2 phosphorylation in dopaminergic neurons in SNc after challenge with the dopaminergic neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a common model for PD. Genetic suppression of CRMP2 phosphorylation by mutation of the obligatory Cyclin‐dependent kinase 5 (Cdk5)‐targeted serine‐522 site prevented axonal degradation in the nigrostriatal pathway of transgenic mice. As a result, the degree of MPTP‐induced motor impairment in the rotarod test was suppressed. These results suggest that suppression of CRMP2 phosphorylation may be a novel therapeutic target for PD.