PMID- 31807952
OWN - NLM
STAT- MEDLINE
DCOM- 20210326
LR  - 20231128
IS  - 1435-1463 (Electronic)
IS  - 0300-9564 (Print)
IS  - 0300-9564 (Linking)
VI  - 127
IP  - 2
DP  - 2020 Feb
TI  - The catecholaldehyde hypothesis: where MAO fits in.
PG  - 169-177
LID - 10.1007/s00702-019-02106-9 [doi]
AB  - Monoamine oxidase (MAO) plays a central role in the metabolism of the 
      neurotransmitters dopamine, norepinephrine, and serotonin. This brief review 
      focuses on 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is the immediate 
      product of MAO acting on cytoplasmic dopamine. DOPAL is toxic; however, normally 
      DOPAL is converted via aldehyde dehydrogenase (ALDH) to 3,4-dihydroxyphenylacetic 
      acid (DOPAC), which rapidly exits the neurons. In addition to vesicular uptake of 
      dopamine via the vesicular monoamine transporter (VMAT), the two-enzyme sequence 
      of MAO and ALDH keeps cytoplasmic dopamine levels low. Dopamine oxidizes readily 
      to form toxic products that could threaten neuronal homeostasis. The 
      catecholaldehyde hypothesis posits that diseases featuring catecholaminergic 
      neurodegeneration result from harmful interactions between DOPAL and the protein 
      alpha-synuclein, a major component of Lewy bodies in diseases such as Parkinson 
      disease, dementia with Lewy bodies, and pure autonomic failure. DOPAL potently 
      oligomerizes alpha-synuclein, and alpha-synuclein oligomers impede vesicular 
      functions, shifting the fate of cytoplasmic dopamine toward MAO-catalyzed 
      formation of DOPAL-a vicious cycle. When MAO deaminates dopamine to form DOPAL, 
      hydrogen peroxide is generated; and DOPAL, hydrogen peroxide, and divalent metal 
      cations react to form hydroxyl radicals, which peroxidate lipid membranes. Lipid 
      peroxidation products in turn inhibit ALDH, causing DOPAL to accumulate-another 
      vicious cycle. MAO inhibition decreases DOPAL formation but concurrently 
      increases the spontaneous oxidation of dopamine, potentially trading off one form 
      of toxicity for another. These considerations rationalize a neuroprotection 
      strategy based on concurrent treatment with an MAO inhibitor and an anti-oxidant.
FAU - Goldstein, David S
AU  - Goldstein DS
AD  - Autonomic Medicine Section, Clinical Neurosciences Program, Division of 
      Intramural Research, National Institute of Neurological, Disorders and Stroke, 
      National Institutes of Health, 9000 Rockville Pike MSC-1620, Building 10 Room 
      8N260, Bethesda, MD, 20892-1620, USA. goldsteind@ninds.nih.gov.
LA  - eng
GR  - ZIA NS003033/ImNIH/Intramural NIH HHS/United States
GR  - ZIA NS003034/ImNIH/Intramural NIH HHS/United States
GR  - ZIA NS003125/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Review
DEP - 20191205
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 5707-55-1 (3,4-dihydroxyphenylacetaldehyde)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
EIN - J Neural Transm (Vienna). 2019 Dec 21;:. PMID: 31865454
MH  - 3,4-Dihydroxyphenylacetic Acid/*analogs & derivatives/*metabolism
MH  - Aldehyde Dehydrogenase/*metabolism
MH  - Animals
MH  - Dopamine/*metabolism
MH  - Humans
MH  - Monoamine Oxidase/*metabolism
MH  - Neurodegenerative Diseases/*metabolism
MH  - Neurons/*metabolism
PMC - PMC10680281
MID - NIHMS1947045
OTO - NOTNLM
OT  - Alpha-synuclein
OT  - DOPAL
OT  - Dopamine
OT  - Monoamine oxidase
EDAT- 2019/12/07 06:00
MHDA- 2021/03/27 06:00
PMCR- 2023/11/27
CRDT- 2019/12/07 06:00
PHST- 2019/10/30 00:00 [received]
PHST- 2019/11/14 00:00 [accepted]
PHST- 2019/12/07 06:00 [pubmed]
PHST- 2021/03/27 06:00 [medline]
PHST- 2019/12/07 06:00 [entrez]
PHST- 2023/11/27 00:00 [pmc-release]
AID - 10.1007/s00702-019-02106-9 [pii]
AID - 10.1007/s00702-019-02106-9 [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2020 Feb;127(2):169-177. doi: 
      10.1007/s00702-019-02106-9. Epub 2019 Dec 5.