Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases

Neurotoxicology. 2004 Jan;25(1-2):101-15. doi: 10.1016/S0161-813X(03)00090-1.

Abstract

The monoamine oxidase (MAO) metabolites of norepinephrine (NE) or epinephrine (EPI) and of dopamine (DA) are 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and 3,4-dihydroxyphenylacetaldehyde (DOPAL), respectively. The toxicity of these catecholamine (CA) MAO metabolites was predicted over 50 years ago. However, until our recent chemical synthesis of these CA aldehyde metabolites, the hypothesis about their toxicity could not be tested. The present paper reviews recent knowledge gained about these compounds. Topics to be reviewed include: chemical synthesis and properties of DOPEGAL and DOPAL; in vitro and in vivo toxicity of CA aldehydes; subcellular mechanisms of toxicity; free radical formation by DOPEGAL versus DOPAL; mechanisms of accumulation of CA aldehydes in Alzheimer's disease (AD) and Parkinson's disease (PD) and potential therapeutic targets in Alzheimer's disease and Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / analogs & derivatives*
  • 3,4-Dihydroxyphenylacetic Acid / chemistry
  • 3,4-Dihydroxyphenylacetic Acid / metabolism*
  • 3,4-Dihydroxyphenylacetic Acid / toxicity
  • Aldehydes / chemistry
  • Aldehydes / metabolism*
  • Aldehydes / toxicity
  • Animals
  • Apoptosis / physiology
  • Catecholamines / chemistry
  • Catecholamines / metabolism*
  • Catecholamines / toxicity
  • Catechols
  • Humans
  • Neurodegenerative Diseases / metabolism*

Substances

  • Aldehydes
  • Catecholamines
  • Catechols
  • 3,4-Dihydroxyphenylacetic Acid
  • 3,4-dihydroxyphenylglycolaldehyde
  • 3,4-dihydroxyphenylacetaldehyde