Catecholaldehyde hypothesis

From Wikipedia, the free encyclopedia

The catecholaldehyde hypothesis is a scientific theory positing that neurotoxic aldehyde metabolites of the catecholamine neurotransmitters dopamine and norepinephrine are responsible for neurodegenerative diseases involving loss of catecholaminergic neurons, for instance Parkinson's disease.^[1]^[2] The specific metabolites thought to be involved include 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), which are formed from dopamine and norepinephrine by monoamine oxidase, respectively.^[1]^[2] These metabolites are subsequently inactivated and detoxified by aldehyde dehydrogenase (ALDH).^[1]^[2] DOPAL and DOPEGAL are monoaminergic neurotoxins in preclinical models and inhibition of and polymorphisms in ALDH are associated with Parkinson's disease.^[1]^[2]^[3]^[4] The catecholaldehyde hypothesis additionally posits that DOPAL oligomerizes with α-synuclein resulting in accumulation of oligomerized α-synuclein (i.e., synucleinopathy) and that this contributes to cytotoxicity.^[1]^[2]^[5]^[3]

References

^ ^a ^b ^c ^d ^e Goldstein DS (February 2020). "The catecholaldehyde hypothesis: where MAO fits in". J Neural Transm (Vienna). 127 (2): 169–177. doi:10.1007/s00702-019-02106-9. PMC 10680281. PMID 31807952.
^ ^a ^b ^c ^d ^e Goldstein DS (June 2021). "The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know". Int J Mol Sci. 22 (11): 5999. doi:10.3390/ijms22115999. PMC 8199574. PMID 34206133.
^ ^a ^b Goldstein DS, Sharabi Y (January 2019). "The heart of PD: Lewy body diseases as neurocardiologic disorders". Brain Res. 1702: 74–84. doi:10.1016/j.brainres.2017.09.033. PMC 10712237. PMID 29030055.
^ Marchitti SA, Deitrich RA, Vasiliou V (June 2007). "Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase". Pharmacol Rev. 59 (2): 125–150. doi:10.1124/pr.59.2.1. PMC 2647328. PMID 17379813.
^ Goldstein DS, Kopin IJ, Sharabi Y (December 2014). "Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders". Pharmacol Ther. 144 (3): 268–282. doi:10.1016/j.pharmthera.2014.06.006. PMC 4591072. PMID 24945828.

Dopamine	3,4-Dihydroxyphenylacetaldehyde (DOPAL) 3,4-Dihydroxyphenylacetic acid (DOPAC) Homovanillyl alcohol Hydroxytyrosol (3,4-dihydroxyphenylethanol; DOPET) 3-Methoxytyramine (3-MT) Homovanillic acid (HVA)
Norepinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) 3,4-Dihydroxymandelic acid (DHMA) Normetanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL) Vanillylmandelic acid (VMA) 3,4-Dihydroxyphenylethylene glycol (DOPEG, DHPG) 3-Methoxy-4-hydroxyphenylglycol (MHPG, MOPEG)
Epinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) Metanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL)

Anabolism	Tryptophan 5-Hydroxytryptophan (5-HTP)
Catabolism	5-Hydroxyindoleacetaldehyde (5-HIAL) 5-Hydroxyindoleacetic acid (5-HIAA) 5-Hydroxytryptophol (5-HTOL)

v t e Monoaminergic neurotoxins
Dopaminergic	2′-CH₃-MPTP (2′-methyl-MPTP) 2,4,5-THA 2,4,5-THMA 5-S-Cysteinyldopamine 5,6-DHT 6-Hydroxydopa 6-OHDA quinone 6,7-DHT ALDH inhibitors (e.g., disulfiram, methylmercury) Amphetamine Benomyl Daidzin Dieldrin DOPA quinone DOPAL DOPAL quinone Dopamine Dopamine quinone Fenpropathrin Haloperidol HPP⁺ HPTP Mancozeb Maneb Mephedrone Methamphetamine Methylone MPP⁺ (cyperquat) MPTP N-Methylnorsalsolinol Norsalsolinol Oxidopamine (6-OHDA) Paraquat Rotenone Salsolinol Ziram
Noradrenergic	2′-NH₂-MPTP (2′-amino-MPTP) 2,4,5-THA 4,5-DHT 5,6-DHT 5,7-DHT 6-Hydroxydopa DOPEGAL DSP-4 MDA (tenamfetamine) Oxidopamine (6-OHDA) Xylamine
Serotonergic	2′-NH₂-MPTP (2′-amino-MPTP) 2,4-DCA 2,4,5-THA 2,4,5-THMA 3-CA 3,4-DCA 4-CAB (α-ethyl-PCA) 4-CMA 4,5-DHT 5-IAI 5-MAPB 5,6-DHT 5,7-DHT 6,7-DHT αET Fenfluramine Haloperidol HHA (α-methyldopamine) HHMA (α-methylepinine, α,N-dimethyldopamine) HPP⁺ HPTP MBDB MDA (tenamfetamine) MDMA (midomafetamine) Mephedrone Methamphetamine Methylone Norfenfluramine PBA PCA PIA
Unsorted	5-HIAL RHPP⁺ RHPTP
See also: Receptor/signaling modulators • Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake inhibitors • Monoamine releasing agents • Monoamine metabolism modulators

This neuroscience article is a stub. You can help Wikipedia by expanding it.

Hidden category: