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Frontiers in Neurology


Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00754

Hypothesis: Novel etiologic and molecular mechanistic leads for sporadic neurodegenerative diseases based on experience with Western Pacific ALS/PDC.

  • 1Department of Neurology, School of Medicine, Oregon Health & Science University, United States

Seventy years of research on Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia (ALS/PDC) has provided invaluable data on the etiology, molecular pathogenesis and latency of this disappearing environmental neurodegenerative disease. ALS/PDC is linked to genotoxic chemicals (notably methylazoxymethanol, MAM) derived from seed of the cycad plant (Cycas spp) which was used as a traditional food and/or medicine in all three affected Western Pacific populations. MAM, nitrosamines and hydrazines generate methyl free radicals which damage DNA (O6-methylguanine) that can induce mutations in cycling cells and degenerative changes of post-mitotic cells, notably neurons. The paper examines evidence that link exposure to naturally occurring and manmade sources of nitrosamines and hydrazines to sporadic forms of ALS (with or without frontotemporal degeneration), progressive supranuclear palsy, and Alzheimer disease. Research approaches are offered to test this unifying hypothesis.

Keywords: Amyotrophic lateral sclerosis ( ALS), Progressive Supranuclear Palsy, Alzheimer Disease, DNA Damage, cycad methylazoxymethanol, Nitrosamines, Hydrazines

Received: 08 Apr 2019; Accepted: 27 Jun 2019.

Edited by:

Vincenzo La Bella, University of Palermo, Italy

Reviewed by:

Savina Apolloni, Fondazione Santa Lucia (IRCCS), Italy
Soledad Matus, Fundación Ciencia and Vida, Chile
Philippe Corcia, Université de Tours, France  

Copyright: © 2019 Spencer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Peter Spencer, Oregon Health & Science University, Department of Neurology, School of Medicine, Portland, 97239, Oregon, United States,