Inhibition of collapsin response mediator protein-2 phosphorylation ameliorates motor phenotype of ALS model mice expressing SOD1G93A

Yurika Numata-Uematsu, Shuji Wakatsuki, Seiichi Nagano, Megumi Shibata, Kazuhisa Sakai, Noritaka Ichinohe, Katsuhiko Mikoshiba, Toshio Ohshima, Naoya Yamashita, Yoshiro Goshima, Toshiyuki Araki

研究成果: Article査読

8 被引用数 (Scopus)

抄録

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurological disease characterized by the selective degeneration of motor neurons leading to paralysis and immobility. Missense mutations in the gene coding for the Cu 2+ /Zn 2+ superoxide dismutase 1 (SOD1) accounts for 15–20% of familial ALS, and mice overexpressing ALS-linked SOD1 mutants have been frequently used as an animal model for ALS. Degeneration of motor neurons in ALS progresses in a manner called “dying back”, in which the degeneration of synapses and axons precedes the loss of cell bodies. Phosphorylation of collapsin response mediator protein 2 (CRMP2) is implicated in the progression of neuronal/axonal degeneration of different etiologies. To evaluate the role of CRMP2 phosphorylation in ALS pathogenesis, we utilized CRMP2 S522A knock-in (CRMP2 ki/ki ) mice, in which the serine residue 522 was homozygously replaced with alanine and thereby making CRMP2 no longer phosphorylatable by CDK5 or GSK3B. We found that the CRMP2 ki/ki /SOD1 G93A mice showed delay in the progression of the motor phenotype compared to their SOD1 G93 -Tg littermates. Histological analysis revealed that the CRMP2 ki/ki /SOD1 G93A mice retained more intact axons and NMJs than their SOD1 G93A -Tg littermates. These results suggest that the phosphorylation of CRMP2 may contribute to the axonal degeneration of motor neurons in ALS.

本文言語English
ページ(範囲)63-68
ページ数6
ジャーナルNeuroscience Research
139
DOI
出版ステータスPublished - 2019 2

ASJC Scopus subject areas

  • Neuroscience(all)

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