In neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases, type B monoamine oxidase
(MAO-B) has been proposed to play a primary role though generating reactive oxygen species in oxidation of monoamine
substrates. MAO-B oxidizes MPTP into MPP+, and an MAO-B inhibitor, deprenyl, prevents the MPTP oxidation and also
MPP+neutotoxicity. These results suggest the association of MAO-B with neuronal death in neurodegenerative disorders.
On the other hand, deprenyl and rasagiline, selective MAO-B inhibitors, have been proved to protect neuronal cells in cellular
and animal models of neurodegeneration. These inhibitors decrease oxidation of the substrates, scavenge oxygen
radicals, intervene apoptosis signal pathway in mitochondria and induce pro-survival genes coding anti-apoptotic Bcl-2
and neurotrophic factors. However, the association of MAO-B itself with the neuroprotective function of MAO-B inhibitors
remains enigmatic. Recently, the involvement of type A MAO (MAO-A) in neuronal death has been shown by upregulation
MAO-A expression in cellular models. MAO-A is a target of an endogenous neurotoxin, Nmethyl(
R)salsolinol, and MAO-A knockdown (KO) with short interfering (si)RNA protects neuronal death from apoptosis.
In addition, MAO-A mediates the increased expression of genes for anti-apoptotic, pro-survival Bcl-2 and neurotrophic
factors by MAO-B inhibitors, whereas MAO-B doe not. In this review, we present our recent results on the novel
role of MAO-A and MAO-B in neuronal death and also in the neuroprotective gene induction by MAO inhibitors. The future
development of new series of neuroprotective drugs is discussed among compounds, which have high affinity to
MAO-A and can induce pro-survival genes. MAO-A is expected to play a role in disease-modifying therapy for neurodegenerative