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

As in Alzheimer's disease, brains of Guam Chamorros with amyotrophic latera l sclerosis (ALS) and Parkinsonism-dementia complex (PDC) contain intraneur onal-paired helical filaments composed of accumulated phosphorylated tau pr otein. Tau mRNA expression in rat neuronal cultures-normally modulated by g lutamate-increases after treatment with the aglycone of cycasin, a cycad-de rived toxin whose concentration in Chamorro food varies with disease incide nce. Elevated Tan gene expression in vitro is coincident with increased cyc asin-related DNA adducts and reduced DNA repair. Cycasin and endogenous glu tamate may together promote the accumulation of tau protein and neuronal de generation in Western Pacific ALS/PDC. (C) 1999 Academic Press.