The guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates Tau mRNA expression and excitotoxicity

Françoise Esclaire, Glen Kisby, Peter Spencer, John Milne, Mathieu Lesort, Jacques Hugon

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

As in Alzheimer's disease, brains of Guam Chamorros with amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) contain intraneuronal-paired helical filaments composed of accumulated phosphorylated tau protein. Tau mRNA expression in rat neuronal cultures-normally modulated by glutamate-increases after treatment with the aglycone of cycasin, a cycad- derived toxin whose concentration in Chamorro food varies with disease incidence. Elevated Tau gene expression in vitro is coincident with increased cycasin-related DNA adducts and reduced DNA repair. Cycasin and endogenous glutamate may together promote the accumulation of tau protein and neuronal degeneration in Western Pacific ALS/PDC.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalExperimental Neurology
Volume155
Issue number1
DOIs
StatePublished - Jan 1999

Keywords

  • DNA adducts
  • DNA repair
  • Glutamate
  • Guam ALS/PDC
  • Tau

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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