Parkinson's disease: the first common neurological disease due to auto-intoxication?
http://qjmed.oxfordjournals.org/cgi/.../full/98/3/215
Parkinson's disease: the first common neurological disease due to auto-intoxication? Parkinson's disease may be a disease of autointoxication. N-methylated pyridines (e.g. MPP+) are well-established dopaminergic toxins, and the xenobiotic enzyme nicotinamide N-methyltransferase (NNMT) can convert pyridines such as 4-phenylpyridine into MPP+, using S-adenosyl methionine (SAM) as the methyl donor. NNMT has recently been shown to be present in the human brain, a necessity for neurotoxicity, because charged compounds cannot cross the blood-brain barrier. Moreover, it is present in increased concentration in parkinsonian brain. This increase may be part genetic predisposition, and part induction, by excessive exposure to its substrates (particularly nicotinamide) or stress. Elevated enzymic activity would increase MPP+-like compounds such as N-methyl nicotinamide at the same time as decreasing intraneuronal nicotinamide, a neuroprotectant at several levels, creating multiple hits, because Complex 1 would be poisoned and be starved of its major substrate NADH. Developing xenobiotic enzyme inhibitors of NNMT for individuals, or dietary modification for the whole population, could be an important change in thinking on primary and secondary prevention. |
NMND found in PD as well as autism
Recent article summary in New Scientist magazine, "Early test could pick out kids at risk of autism" concerns use of Nuclear magnetic resonance spectroscopy of urine in children and discovered a distinct "chemical fingerprint" in the group with autism. this signature is related directly to: GUT BACTERIA. The urine testing shows high levels of metabolites of gut bacteria, raising the question of whether gut bacteria are implicated in the etiology of autism--or at least asking why these levels are high in autism. also may provide an objective measurement for autism in kids. Noted in the article: "It is possible that the gut bacteria in children with autism are producing toxins that might interfere with brain development. One of the compounds identified in the urine...was N-methyl nicotinamide (NMND) which has also been implicated in Parkinson's Disease...[researchers] found that short chain fatty acids produced by clostridium bacteria can induce reversible autism like behaviors in rats..."
Linda Geddes, "Early test could pick out kids at risk of autism"New Scientist, June 12, 2010, p.9. |
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