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

Kentaro Togashi, Masaya Hasegawa, Jun Nagai, Aine Tonouchi, Daiki Masukawa, Kenneth Hensley, Yoshio Goshima, Toshio Ohshima

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalGenes to Cells
Volume24
Issue number1
DOIs
Publication statusPublished - 2019 Jan

Keywords

  • CRMP2 phosphorylation
  • Parkinson’s disease
  • dopaminergic neuron

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this