Monoamine oxidase B, smoking, and Parkinson's disease

Abstract

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.