Aizawa H, Sawada J, Hideyama T, Yamashita T, Katayama T, Hasebe N, Kimura T, Yahara O, Kwak S. TDP-43 pathology in sporadic ALS occurs in motor neurons lacking the RNA editing enzyme ADAR2. Acta Neuropathol. 2010 Jul;120(1):75-84. PubMed.
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Amber Dance has nicely summarized both papers. Concerning the Cucchiaroni paper, I believe it is a very important contribution to the literature. Deborah Mash, John Pablo, and colleagues have recently confirmed prior studies by Paul Cox and colleagues that BMAA is accumulated in the brains of patients with Alzheimer disease. They also showed that BMAA is accumulated in the brains of patients with amyotrophic lateral sclerosis, but not in brains of control patients or those with Huntington disease. They have obtained preliminary evidence that BMAA is accumulated in the brains of patients with Parkinson disease.
The concentration of BMAA in the protein-bound fraction of the brains of Chamorros with ALS/PDC is of the order of 5 mM, while that in the brains of patients with AD, PD, and ALS is approaching 1 mM. However, Cox and colleagues found that the concentration of BMAA in the soluble fraction of the brains of Chamorros with ALS/PDC was about 50 micromolar.
The paper by Cucchiaroni et al. demonstrates a significant physiological effect of BMAA on dopaminergic neurons. It suggests that a major source of this effect is via the GluR1 subunit and provides a vital link in the pathway from the environmental neurotoxin—BMAA derived from ubiquitous cyanobacteria—to the human diseases AD, PD, and ALS. However, it should be noted that the concentrations used in the study were in the mM range; more chronic, lower-dose studies are needed to simulate the apparent state in humans.
The field of cyanobacterial BMAA and its role in human neurodegenerative diseases was recently reviewed in a supplement to the journal ALS.
See also:
Bradley, W.G., Cox, P.A. Supplement 2. Amyotrophic Lateral Sclerosis. June 2009;10:1-128.
References:
Pablo J, Banack SA, Cox PA, Johnson TE, Papapetropoulos S, Bradley WG, Buck A, Mash DC. Cyanobacterial neurotoxin BMAA in ALS and Alzheimer's disease. Acta Neurol Scand. 2009 Oct;120(4):216-25. PubMed.
Murch SJ, Cox PA, Banack SA, Steele JC, Sacks OW. Occurrence of beta-methylamino-l-alanine (BMAA) in ALS/PDC patients from Guam. Acta Neurol Scand. 2004 Oct;110(4):267-9. PubMed.
Murch SJ, Cox PA, Banack SA. A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12228-31. PubMed.
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