protein
Aldehyde dehydrogenase 1A1
Gene
ALDH1A1
Organism
Homo sapiens(9606)
Length
501 aa
Mass
54,862 Da
Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acids (UniProt: P00352). The enzyme plays multiple roles: it catalyzes the second step in conversion of retinol to retinoic acid, detoxifies aldehydes from lipid peroxidation such as 4-hydroxynon-2-enal, and participates in fructosamine degradation. Through aminobutyraldehyde dehydrogenase activity, it also contributes to GABAergic neurotransmission in the midbrain.
ALDH1A1 is widely distributed in tissues and participates in critical metabolic pathways controlling retinoid homeostasis and cellular detoxification. No baseline disease association is documented in UniProt, though the protein's role in clearing oxidative stress metabolites suggests broader cellular protection functions.
In Alzheimer's disease, ALDH1A1 is significantly upregulated in post-mortem AD brain compared to age-matched controls, with a mean log2 fold-change of 0.541 (Chaparral AD proteomics). This elevation may reflect increased oxidative stress and lipid peroxidation in the AD brain, requiring enhanced detoxification capacity. The upregulation was detected across one analyzed subcellular fraction in a TMT-labeled proteomics study.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+0.541
S3
not detected
Mean log₂FC across detected fractions: +0.541 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:19296407, PubMed:25450233, PubMed:26373694). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (By similarity). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:12941160, PubMed:15623782, PubMed:19296407). Also functions downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (PubMed:17175089). Also has an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity)
Sources
Last updated 5/8/2026, 6:34:35 AM
