期刊
JOURNAL OF CLINICAL NEUROSCIENCE
卷 12, 期 1, 页码 6-11出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jocn.2004.10.002
关键词
MPP; nicotinamide; NNMT; NAD; Parkinson's disease; xenobiotics; autotoxicity
Xenobiotic enzymes normally protect against toxins but on occasion can convert protoxins into toxins. N-methylated pyridines (such as the N-methyl-4 phenylpyridinium ion (MPP+)) are well-established dopaminergic toxins. The enzyme nicotinamide N-methyltransferase (NNMT) can covert otherwise harmless pyridines such as 4-phenylpyridine into MPP+ like compounds. This enzyme has recently been shown to be present in the human brain, which is a necessity for neurotoxicity, as charged compounds such as MPP+ cannot cross the blood brain barrier. Moreover, it is present in increased concentration in the brain of patients with Parkinson's disease (PD). This would increase MPP+ like compounds at the same time as decreasing intraneuronal nicotinamide, a neuroprotectant at several levels, thus creating a multiple hit, as additionally complex 1 of the mitochondrial complex would also be poisoned and starved of its major substrate, nicotinamide adenine dinucleoticle (NAD). Thus, PD may be a disease of auto intoxication. Xenobiotic enzyme inhibitors of NNMT, with or without dietary modification, would be a novel way to attempt primary prevention of PD. (C) 2004 Elsevier Ltd. All rights reserved.
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