Early decrease of survival signal-related proteins in spinal motor neurons of presymptomatic transgenic mice with a mutant SOD1 gene

H. Warita, Y. Manabe, T. Murakami, Y. Shiro, I. Nagano, K. Abe

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The mechanisms of motor neuronal death in amyotrophic lateral sclerosis (ALS) remain to be unclear. Phosphatidylinositol 3-kinase (PI3-K) and its main downstream effector, Akt/protein kinase B (PKB) have been shown to play a central role in neuronal survival against apoptosis supported by neurotrophic factors. In order to investigate a possible impairment of survival signaling, we examined expressions of PI3-K and Akt in the spinal cord of the transgenic mice overexpressing a mutant Cu/Zn superoxide dismutase (SOD1) gene, a valuable model for human ALS. Immunoblotting and immunohistochemical analyses showed that the majority of spinal motor neurons lost the immunoreactivities for both PI3-K and Akt in the early and presymptomatic stage that preceded significant loss of the neurons. The present results suggest that an early decrease of survival signal proteins in the spinal motor neurons may account for the subsequent motor neuronal loss in this animal model of ALS.

Original languageEnglish
Pages (from-to)345-352
Number of pages8
JournalApoptosis
Volume6
Issue number5
DOIs
Publication statusPublished - Jan 1 2001

Keywords

  • ALS
  • Akt
  • Phosphatidylinositol 3-kinase
  • SOD1
  • Transgenic mouse

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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