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Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

[ Vol. 12 , Issue. 20 ]

Author(s):

Darrell D. Mousseau and Glen B. Baker   Pages 2163 - 2176 ( 14 )

Abstract:


Historically, much of the focus on monoamine oxidases and their substrates has been in the area of depression and the monoamine neurotransmitters serotonin (5-hydroxytryptamine), noradrenaline, and to a lesser extent, dopamine. With both forms of monoamine oxidase (A and B), the production of hydrogen peroxide as a byproduct of the reaction between the monoamine oxidases and their monoamine substrates has also implicated monoamine oxidase-sensitive events in intrinsic cell death pathways, particularly those centered on oxidative stress and peroxyradical-mediated mechanisms. Consequently, and perhaps not unexpectedly, the inhibition of monoamine oxidase has been considered as adjunctive therapy in neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, both of which involve a significant oxidative stress component. Yet the literature also provides ambiguities; indeed, not all of the functions of monoamine oxidases are dependent on catalytic activity nor can they all be ascribed to expression levels of the monoamine oxidase protein per se. Recent reports strongly suggest that the functions of monoamine oxidases also rely on posttranslational modifications, epigenetic influences, interactions with other proteins, the cell phenotype and its localization to specific subcellular compartments. These recent developments certainly complicate the issue, yet they need to be duly considered when implicating monoamine oxidases and their inhibitors in both in vitro and in vivo pathological contexts.

Keywords:

Monoamine oxidase, oxidative stress, apoptosis, phosphorylation, splice variant, catalytic independent, mitochondria, nucleus, Alzheimer disease, Parkinson’s disease

Affiliation:

Cell Signalling Laboratory, GB41 HSB, University of Saskatchewan, 107 Wiggins Rd., Saskatoon, SK, S7N 5E5, Canada.



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