Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases.
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.
Burke
William J
WJ
Department of Neurology, Veterans Affairs Medical Center, Saint Louis University Health Sciences Center, St. Louis, MO 63110, USA. althagml@slucare1.sluh.edu
Li
Shu Wen
SW
Chung
Hyung D
HD
Ruggiero
David A
DA
Kristal
Bruce S
BS
Johnson
Eugene M
EM
Lampe
Patricia
P
Kumar
Vijaya B
VB
Franko
Mark
M
Williams
Evelyn A
EA
Zahm
Daniel S
DS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002395:Catecholamines / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002396:Catechols; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*
D000447:Aldehydes; D002395:Catecholamines; D002396:Catechols; D015102:3,4-Dihydroxyphenylacetic Acid; C007431:3,4-dihydroxyphenylglycolaldehyde; C007430:3,4-dihydroxyphenylacetaldehyde