title: Is neurodegenerative disease a long-latency response to early-life genotoxin exposure?
abstract: Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex, a disappearing neurodegenerative disease linked to use of the neurotoxic cycad plant for food and/or medicine, is intensively studied because the neuropathology (tauopathy) is similar to that of Alzheimer's disease. Cycads contain neurotoxic and genotoxic principles, notably cycasin and methylazoxymethanol, the latter sharing chemical relations with nitrosamines, which are derived from nitrates and nitrites in preserved meats and fertilizers, and also used in the rubber and leather industries. This review includes new data that influence understanding of the neurobiological actions of cycad and related genotoxins and the putative mechanisms by which they might trigger neurodegenerative disease.
authors.affiliation: Department of Basic Medical Sciences, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, OR 97355, USA. gkisby@westernu.edu
authors.forename: Glen E
authors.initials: GE
authors.lastname: Kisby
authors.forename: Peter S
authors.initials: PS
authors.lastname: Spencer
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced* / Q000453:epidemiology; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D029784:Cycas / Q000737:chemistry*; D003492:Cycasin / Q000494:pharmacology / Q000633:toxicity; D004249:DNA Damage; D006027:Glycosides / Q000494:pharmacology / Q000633:toxicity; D006141:Guam / Q000453:epidemiology; D006801:Humans; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D009153:Mutagens / Q000494:pharmacology / Q000633:toxicity*; D009498:Neurotoxins / Q000494:pharmacology / Q000633:toxicity*; D010139:Pacific Islands / Q000453:epidemiology; D024801:Tauopathies / Q000453:epidemiology / Q000209:etiology
chemical_list: D006027:Glycosides; D009153:Mutagens; D009498:Neurotoxins; D008746:Methylazoxymethanol Acetate; D003492:Cycasin; C030667:methylazoxymethanol
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