The involvement of Monominoxidase A (MAO-A) in neurodegeneration beyond the oxidative stress mechanism

Monoamine oxidase (MAO) - a mitochondrial flavoenzyme - catalyzes the oxidative deamination of dietary and biogenic monoamines. It is located at the outer membrane of mitochondria in the brain and peripheral tissues. According to substrate selectivity, two isoenzymes have been known for MAO, named MAO-A and MAO-B. These isoenzymes generate reactive oxygen species during oxidation of monoamine neurotransmitters such as norepinephrine, dopamine, and serotonin and have a pivotal role in neuronal death in neurodegenerative disorders by the potentiation of the oxidative stress mechanism. However, studies have recently indicated the up-regulation of the MAO-A gene and protein expression in different models of neuronal cell death, which suggests a prominent role of MAO-A in cell death signaling. Also, knockdown of the MAO-A gene in neuronal cells protects them from apoptosis, which confirms the association of MAO-A in neuronal death. MAO-B inhibitors like Rasagyline and Deprenyl have been shown to protect neuronal cells in neurodegeneration models. These inhibitors can reduce the production of oxygen radicals through inhibition of monoamine oxidation. Moreover, they activate cellular pro-survival signaling pathways through the induction of the Bcl-2 gene, an anti-apoptotic factor, and neurotrophic factors. The studies have indicated that the latter effect of MAO-B inhibitors is mediated through binding to MAO-A.In the present study, the role of MAO-A in neuronal death signaling pathways and the association of MAO-A in neuroprotection by MAO-B inhibitors are reviewed.