Monoamine oxidase B, smoking, and Parkinson's disease.
Idiopathic Parkinson's disease (PD) has been reported to occur more commonly among non-smokers than among cigarette smokers, for reasons that are unknown. PD may possibly be caused by one or more unidentified neurotoxins which chemically resemble N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a substance which after conversion to an active neurotoxin by monoamine oxidase B (MAO-B) can extensively damage dopaminergic nigrostriatal neurons in humans, lower primates and mice. We measured MAO-B in autopsied brain of PD patients and control subjects and found enzyme activities similar. Inhibition of rat liver MAO-B by the urines of PD patients was greater than by urines of control subjects. These observations do not favour the hypothesis that idiopathic PD is due to excessive conversion of a precursor compound to an active neurotoxin by MAO-B. On the other hand, we found that MAO-B activity was significantly lower in the platelets of heavy cigarette smokers than in platelets of non-smokers. Finally, we found that hydrazine, a compound present in tobacco smoke, had a significant effect in mice in protecting dopaminergic nigrostriatal neurons from damage by MPTP. If idiopathic PD is caused by MPTP-like neurotoxins, accumulation of hydrazine in the tissues of cigarette smokers might explain their reduced likelihood of developing PD.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D010300:Parkinson Disease / Q000209:etiology*; D011725:Pyridines / Q000037:antagonists & inhibitors; D012907:Smoking; D013861:Thiocyanates / Q000494:pharmacology
D006834:Hydrazines; D007527:Isoenzymes; D011725:Pyridines; D013861:Thiocyanates; C029424:hydrazine; D009538:Nicotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase