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 Citations (Scopus)

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

Fingerprint

Cycasin
Guam
DNA Damage
tau Proteins
Amyotrophic Lateral Sclerosis
Parkinsonian Disorders
Messenger RNA
Glutamic Acid
DNA Adducts
DNA Repair
Dementia
Alzheimer Disease
Gene Expression
Food
Incidence
Brain
methylazoxymethanol

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

The guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates Tau mRNA expression and excitotoxicity. / Esclaire, Françoise; Kisby, Glen; Spencer, Peter; Milne, John; Lesort, Mathieu; Hugon, Jacques.

In: Experimental Neurology, Vol. 155, No. 1, 01.1999, p. 11-21.

Research output: Contribution to journalArticle

Esclaire, Françoise ; Kisby, Glen ; Spencer, Peter ; Milne, John ; Lesort, Mathieu ; Hugon, Jacques. / The guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates Tau mRNA expression and excitotoxicity. In: Experimental Neurology. 1999 ; Vol. 155, No. 1. pp. 11-21.
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