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Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure?
Department of Basic Medical Sciences, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, OR 97355, USA
Global Health Center, Center for Research on Occupational & Environmental Toxicology, and School of Medicine Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA
* Author to whom correspondence should be addressed.
Received: 9 August 2011; in revised form: 9 September 2011 / Accepted: 15 September 2011 / Published: 29 September 2011
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.
Keywords: Guam; cycad; methylazoxymethanol (MAM); b-N-methylamino-L-alanine (L-BMAA); DNA damage; tauopathy; neurodegenerative disease; amyotrophic lateral sclerosis (ALS); parkinsonism-dementia; nitrosamines; formaldehyde
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Kisby, G.E.; Spencer, P.S. Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure? Int. J. Environ. Res. Public Health 2011, 8, 3889-3921.
Kisby GE, Spencer PS. Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure? International Journal of Environmental Research and Public Health. 2011; 8(10):3889-3921.
Kisby, Glen E.; Spencer, Peter S. 2011. "Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure?" Int. J. Environ. Res. Public Health 8, no. 10: 3889-3921.