The Guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates tau mRNA expression and excitotoxicity

Exp Neurol. 1999 Jan;155(1):11-21. doi: 10.1006/exnr.1998.6962.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA Damage* / physiology
  • DNA Repair / physiology
  • Guam
  • Methylazoxymethanol Acetate / analogs & derivatives*
  • Methylazoxymethanol Acetate / poisoning
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotoxins / metabolism*
  • Plants, Toxic / chemistry
  • RNA, Messenger / metabolism*
  • Rats / embryology
  • tau Proteins / genetics*
  • tau Proteins / physiology

Substances

  • Neurotoxins
  • RNA, Messenger
  • tau Proteins
  • Methylazoxymethanol Acetate
  • methylazoxymethanol