Monoamine Oxidase Inhibitor (MAO-I)-Mediated Neuroprotection for Treating Parkinson’s Disease

Toshiharu Nagatsu, Akira Nakashima

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Monoamine oxidases (MAO)-A andMAO-B catalyze the oxidative deamination of monoamine neurotransmitters, such as dopamine (DA), noradrenaline, and serotonin, in the central and peripheral nervous system. Parkinson’s disease (PD) is an aging-related movement disorder, caused by a deficiency of the neurotransmitter DA in the striatum of the brain, caused by degeneration of the nigrostriatal DA neurons. During the1960s, L-DOPA, a direct precursor of DA, which is synthesized in vivo from tyrosine in DA neurons by tyrosine hydroxylase and is converted to DA by aromatic L-amino acid decarboxylase, was introduced to treat this DA deficiency in the striatum. In addition to L-DOPA as a treatment, MAO-B inhibitors (MAO-B-Is) have been used since the 1970s, first selegiline (L-(-)-deprenyl), then rasagiline, and more recently safinamide, as an effective therapy for PD by preventing the degradation of DA. Furthermore, monotherapy with MAO-B-I, selegiline, rasagiline, or safinamide has been proved to be effective in the case of early PD. Accumulating data suggest thatMAO-B-Is may also have neuroprotective efficacy due to several mechanisms that may or may not be related to MAO inhibition. DA oxidation and formation of misfolded α-synuclein oligomers may be linked to dysfunctions of mitochondria, the autophagy-lysosomal system, and ubiquitin-proteasome system, resulting in DA neuron death in PD; and MAO-I may prevent these processes to afford neuroprotection. However, many clinical and basic studies have suggested, but not yet convincingly proved, neuroprotective effects of MAO-I in PD. It remains to be proved if the administration of MAO-B-I several decades before the onset of PD could prevent the occurrence of PD based on neuroprotection and, if so, to confirm the molecular mechanism involved.

Original languageEnglish
Title of host publicationNeuroPsychopharmacotherapy
PublisherSpringer International Publishing
Pages3127-3147
Number of pages21
ISBN (Electronic)9783030620592
ISBN (Print)9783030620585
DOIs
Publication statusPublished - 01-01-2022

All Science Journal Classification (ASJC) codes

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Medicine

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