Tobacco leaf, smoke and smoking, MAO inhibitors, Parkinson's disease and neuroprotection; are there links?

The potential neuroprotective properties of monoamine oxidase B (MAO-B) inhibitors have been of interest in part because of the role that this enzyme plays in the bioactivation of the parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Interestingly, tobacco smokers have lowered levels of brain and blood platelet MAO-B activity and a well documented lowered incidence of Parkinson's disease (PD) compared to non-smokers. This correlation has led to the intriguing question of whether there are possible relationships between smoking, MAO-B activity and PD. Recent studies have evaluated specific components of tobacco smoke for their MAO inhibiting and neuroprotective properties. This chapter summarizes the relevant literature relating to the basic questions in these areas. We have undertaken studies to identify possible inhibitors of MAO-B in the tobacco leaf and tobacco smoke and have evaluated one such compound in the MPTP PD mouse model. In this chapter we report on the results of these studies and present a discussion of potential avenues of research and their implication with respect to PD, smoking and monoamine oxidase.