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Brain monoamine oxidase (MAO) B: a unique neurotoxin and neurotransmitter producing enzyme

M B Youdim1

  • 1Rappaport Family Research Institute, Technion Faculty of Medicine, Department of Pharmacology, Haifa, Israel.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|January 1, 1989
PubMed

Insights

Monoamine oxidase-B (MAO-B) can activate inert amines into neuroactive substances. This challenges the view of MAO-B as only inactivating neurotransmitters and offers new therapeutic strategies.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Monoamine oxidase (MAO) traditionally viewed as solely inactivating neurotransmitters.
  • Emerging evidence suggests MAO-B has broader substrate capabilities.

Purpose of the Study:

  • To re-evaluate the functional role of MAO-B beyond neurotransmitter inactivation.
  • To investigate MAO-B's capacity to oxidize non-polar amines into neuroactive compounds.

Main Methods:

  • Enzymatic assays using MAO-B.
  • Oxidation of specific inert non-polar amine substrates, including MPTP and milacemide.
  • Analysis of reaction products for neuroactivity.

Main Results:

  • MAO-B oxidizes N-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP) to MPP+, a Parkinsonism-inducing dopaminergic neurotoxin.
  • MAO-B also oxidizes milacemide to glycine, an inhibitory amino acid neurotransmitter.
  • Demonstrates MAO-B's capability to generate both neurotoxic and neuroactive substances from inert precursors.

Conclusions:

  • The function of MAO-B is not limited to neurotransmitter inactivation.
  • MAO-B plays a critical role in the bioactivation of certain xenobiotics and endogenous compounds.
  • Selective MAO-B inhibitors and substrates present novel therapeutic avenues for neuropsychiatric disorders.

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