Biology:Catecholaldehyde hypothesis
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]
See also
- Amyloid hypothesis
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "The catecholaldehyde hypothesis: where MAO fits in". J Neural Transm (Vienna) 127 (2): 169–177. February 2020. doi:10.1007/s00702-019-02106-9. PMID 31807952.
- ↑ 2.0 2.1 2.2 2.3 2.4 "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. June 2021. doi:10.3390/ijms22115999. PMID 34206133.
- ↑ 3.0 3.1 "The heart of PD: Lewy body diseases as neurocardiologic disorders". Brain Res 1702: 74–84. January 2019. doi:10.1016/j.brainres.2017.09.033. PMID 29030055.
- ↑ "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. June 2007. doi:10.1124/pr.59.2.1. PMID 17379813.
- ↑ "Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders". Pharmacol Ther 144 (3): 268–282. December 2014. doi:10.1016/j.pharmthera.2014.06.006. PMID 24945828.
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