Death by MAO

Neuronal apoptosis plays a critical role in the development of the nervous system and in neurodegenerative disease. In the Early Edition of the Proceedings of the National Academy of Sciences, De Zutter and Davis report a study of pro-apoptotic, neuronal gene expression and the identification of monoamine oxidase (MAO) as a death-inducing gene. They used the well-studied neuronal pheochromocytoma PC12model, which undergoes apoptosis when deprived of neurotrophic growth factor (NGF). The authors employed subtractive hybridization to identify the A isoform of MAO which was induced 4-fold upon NGF withdrawal. They showed that MAO expression is dependent on p38 MAP kinase signaling. NGF withdrawal increased MAO activity and a MAO inhibitor reduced apoptosis. Furthermore, inhibiting MAO activity also blocked apoptosis induced by the neurotransmitter dopamine, a substrate for MAO deamination.