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

doi:10.1006/exnr.1998.6962

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

Neurology

Research output: Contribution to journal › Article › peer-review

65 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 language	English (US)
Pages (from-to)	11-21
Number of pages	11
Journal	Experimental Neurology
Volume	155
Issue number	1
DOIs	https://doi.org/10.1006/exnr.1998.6962
State	Published - Jan 1999

Keywords

DNA adducts
DNA repair
Glutamate
Guam ALS/PDC
Tau

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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10.1006/exnr.1998.6962

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title = "The guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates Tau mRNA expression and excitotoxicity",

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.",

keywords = "DNA adducts, DNA repair, Glutamate, Guam ALS/PDC, Tau",

author = "Fran{\c c}oise Esclaire and Glen Kisby and Peter Spencer and John Milne and Mathieu Lesort and Jacques Hugon",

note = "Funding Information: Supported by the French Ministry of Health (PHRC), French Ministry of National Education and Research, the Limousin Regional Council, and Grant NS 19611 from the NIH, U.S.A. Dr. D. Henner is thanked for the generous gift of the antibody to human APE and recombinant humanAPE. DanAustin is thanked for technical assistance.",

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AU - Kisby, Glen

AU - Spencer, Peter

AU - Milne, John

AU - Lesort, Mathieu

AU - Hugon, Jacques

N1 - Funding Information: Supported by the French Ministry of Health (PHRC), French Ministry of National Education and Research, the Limousin Regional Council, and Grant NS 19611 from the NIH, U.S.A. Dr. D. Henner is thanked for the generous gift of the antibody to human APE and recombinant humanAPE. DanAustin is thanked for technical assistance.

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N2 - 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.

AB - 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.

KW - DNA adducts

KW - DNA repair

KW - Glutamate

KW - Guam ALS/PDC

KW - Tau

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

Abstract

Keywords

ASJC Scopus subject areas

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