Early decrease of survival factors and DNA repair enzyme in spinal motor neurons of presymptomatic transgenic mice that express a mutant SOD1 gene

Isao Nagano, Tetsuro Murakami, Yasuhiro Manabe, Koji Abe

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The primary pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS) have been elusive. Some of the mechanisms would be implicated in an imbalance between death and survival factors, and impairment of DNA repair possibly caused by oxidative stress. Phosphatidylinositol 3-kinase (PI3-K) and its downstream effector, Akt/protein kinase B (PKB), have been shown to play a pivotal role in neuronal survival against apoptosis supported by neurotrophic factors. To elucidate the mechanisms of motor neuron death in ALS, we examined the expression of PI3-K, Akt, and the DNA repair enzyme redox factor-1 (Ref-1) protein in the spinal cord of transgenic mice with an ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) gene, a valuable model for human ALS. Immunoblotting and immunocytochemical analyses showed that most spinal motor neurons lost immunoreactivity for PI3-K, Akt, and Ref-1 in the presymptomatic stage that preceded a significant loss of neurons. These results suggest that an early decrease of survival signal proteins and a DNA repair enzyme in the spinal motor neurons may account for the mutant SOD1-mediated motor neuron death in this animal model of ALS.

Original languageEnglish
Pages (from-to)541-548
Number of pages8
JournalLife Sciences
Volume72
Issue number4-5
DOIs
Publication statusPublished - Dec 20 2002

Fingerprint

DNA Repair Enzymes
Amyotrophic Lateral Sclerosis
Motor Neurons
Transgenic Mice
Neurons
Phosphatidylinositol 3-Kinase
Genes
Survival
Oxidation-Reduction
Proto-Oncogene Proteins c-akt
Oxidative stress
Nerve Growth Factors
Immunoblotting
DNA Repair
Spinal Cord
Animals
Proteins
Oxidative Stress
Repair
Animal Models

Keywords

  • Akt
  • ALS
  • DNA repair enzyme
  • Phosphatidylinositol 3-kinase
  • Redox factor
  • SOD1
  • Transgenic mouse

ASJC Scopus subject areas

  • Pharmacology

Cite this

Early decrease of survival factors and DNA repair enzyme in spinal motor neurons of presymptomatic transgenic mice that express a mutant SOD1 gene. / Nagano, Isao; Murakami, Tetsuro; Manabe, Yasuhiro; Abe, Koji.

In: Life Sciences, Vol. 72, No. 4-5, 20.12.2002, p. 541-548.

Research output: Contribution to journalArticle

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