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Formaldehyde, DNA damage, ALS and related neurodegenerative diseases

2018; Elsevier BV; Volume: 391; Linguagem: Inglês

10.1016/j.jns.2018.05.017

1878-5883

Peter S. Spencer,

Alcoholism and Thiamine Deficiency

Carmel Armon argues that causation of disease can be ascertained by application of classical methods of epidemiological inference, and he draws on information gleaned from experience with familial, sporadic and Western Pacific forms of ALS. He concludes that disease in all cases begins with DNA damage in single neurons, probably Betz cells, from which it spreads through the neuronal network by an undefined mechanism. By analogy, he draws on the methods of John Snow, who identified the source of London's 1854 cholera epidemic and, in the 20th century, on Richard Doll and Bradford Hill's reasoning that linked cigarette smoking to lung cancer. Armon assembles evidence to support his assertion that smoking is the most plausible risk factor for ALS, and by implication, that one or more chemicals in cigarette smoke induces cumulative DNA damage in both cycling and non-cycling cells, the former triggering carcinogenesis, the latter neuronal degeneration. This bold hypothesis is precisely in line with our earlier conclusions from extensive field and laboratory study of Western Pacific ALS and parkinsonism-dementia (ALS-PDC), a disappearing environmental neurodegenerative disease once hyperendemic among Chamorro residents of Guam and Rota, Japanese living in Kii Peninsula of Honshu Island, and Auyu and Jaqai New Guinean linguistic groups of West Papua, Indonesia. The only common risk factor for ALS-PDC among these three genetically distinct populations is traditional use for food (Guam) and/or medicine (Guam, Kii-Japan, West Papua) of seed of cycads (Cycas spp.), which contain at least two neurotoxic molecules, namely the excitotoxin beta-N-methylamino-l-alanine (L-BMAA) and the genotoxin cycasin (methylazoxymethanol(MAM)-glucoside).