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]

Chemical structure of DOPAL.

See also

• Amyloid hypothesis