3,4-Dihydroxyphenylacetaldehyde

DOPAL is known to be a dopaminergic neurotoxin.{{cite journal | vauthors = Goldstein DS | title = The catecholaldehyde hypothesis: where MAO fits in | journal = J Neural Transm (Vienna) | volume = 127 | issue = 2 | pages = 169–177 | date = February 2020 | pmid = 31807952 | pmc = 10680281 | doi = 10.1007/s00702-019-02106-9 | url = }}{{cite journal | vauthors = Goldstein DS | title = The "Sick-but-not-Dead" Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases | journal = Semin Neurol | volume = 40 | issue = 5 | pages = 502–514 | date = October 2020 | pmid = 32906170 | pmc = 10680399 | doi = 10.1055/s-0040-1713874 | url = }}{{cite journal | vauthors = Goldstein DS | title = The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know | journal = Int J Mol Sci | volume = 22 | issue = 11 | date = June 2021 | page = 5999 | pmid = 34206133 | pmc = 8199574 | doi = 10.3390/ijms22115999 | doi-access = free | url = }} It is much more potent in this regard than dopamine itself and other metabolites of dopamine. According to the catecholaldehyde hypothesis, DOPAL plays a role in aging-related dopaminergic neurodegeneration and in the pathogenesis of Parkinson's disease.{{cite journal | doi = 10.1111/jnc.12345 | title = Determinants of buildup of the toxic dopamine metabolite DOPAL in Parkinson's disease | date = 2013 | last1 = Goldstein | first1 = David S. | last2 = Sullivan | first2 = Patti | last3 = Holmes | first3 = Courtney | last4 = Miller | first4 = Gary W. | last5 = Alter | first5 = Shawn | last6 = Strong | first6 = Randy | last7 = Mash | first7 = Deborah C. | last8 = Kopin | first8 = Irwin J. | last9 = Sharabi | first9 = Yehonatan | journal = Journal of Neurochemistry | volume = 126 | issue = 5 | pages = 591–603 | pmid = 23786406 | pmc = 4096629 }} DOPAL is detoxified mainly by aldehyde dehydrogenase (ALDH). DOPAL is a metabolite of dopamine formed by monoamine oxidase (MAO). In differentiated neuronal cells of the PC12 line, physiological concentrations of DOPAL in isolated mitochondria were highly potent in inducing a pathway associated with programmed cell death (or apoptosis), permeability transition. This suggests the cytotoxity of DOPAL and its role in the progression of Parkinson's disease, which has long been associated with mitochondrial abnormalities and neurotoxicity by way of dopaminergic compounds, while reducing the emphasis on other dopamine derivatives and metabolites.{{cite journal | doi = 10.1016/s0891-5849(01)00484-1 | title = Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria | date = 2001 | last1 = Kristal | first1 = B. | last2 = Conway | first2 = A. D. | last3 = Brown | first3 = A. M. | last4 = Jain | first4 = J. C. | last5 = Ulluci | first5 = P. A. | last6 = Li | first6 = S. W. | last7 = Burke | first7 = W. J. | journal = Free Radical Biology and Medicine | volume = 30 | issue = 8 | pages = 924–931 | pmid = 11295535 }}

Aldehyde dehydrogenase inhibitors (ALDH inhibitors), which prevent the catabolism of DOPAL and thereby increase DOPAL levels, can produce dopaminergic neurotoxicity or augment dopaminergic neurodegeneration.{{cite journal | vauthors = Masato A, Plotegher N, Boassa D, Bubacco L | title = Impaired dopamine metabolism in Parkinson's disease pathogenesis | journal = Mol Neurodegener | volume = 14 | issue = 1 | pages = 35 | date = August 2019 | pmid = 31488222 | pmc = 6728988 | doi = 10.1186/s13024-019-0332-6 | doi-access = free | url = }}{{cite journal | vauthors = Doorn JA, Florang VR, Schamp JH, Vanle BC | title = Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons | journal = Parkinsonism Relat Disord | volume = 20 Suppl 1 | issue = 1 | pages = S73–S75 | date = January 2014 | pmid = 24262193 | pmc = 3932615 | doi = 10.1016/S1353-8020(13)70019-1 | url = }}{{cite journal | vauthors = Legros H, Dingeval MG, Janin F, Costentin J, Bonnet JJ | title = Toxicity of a treatment associating dopamine and disulfiram for catecholaminergic neuroblastoma SH-SY5Y cells: relationships with 3,4-dihydroxyphenylacetaldehyde formation | journal = Neurotoxicology | volume = 25 | issue = 3 | pages = 365–375 | date = March 2004 | pmid = 15019299 | doi = 10.1016/S0161-813X(03)00148-7 | bibcode = 2004NeuTx..25..365L | url = }} Examples of ALDH inhibitors include disulfiram and other known dopaminergic neurotoxins including benomyl, daidzin, dieldrin, methylmercury, rotenone, and ziram. DOPAL itself is also known to inhibit ALDH at high concentrations (>5{{nbsp}}μM).

• 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL)
• 5-Hydroxyindoleacetaldehyde (5-HIAL)

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{{Neurotransmitter metabolism intermediates}}

{{Monoamine neurotoxins}}

{{DEFAULTSORT:Dihydroxyphenylacetaldehyde, 3, 4-}}

Category:Aldehyde dehydrogenase inhibitors

Category:Aldehydes

Category:Catechols

Category:Monoaminergic neurotoxins

Category:Phenolic human metabolites