protein
Alpha-aminoadipic semialdehyde dehydrogenase
aka Alpha-AASA dehydrogenase
Gene
ALDH7A1
Organism
Homo sapiens(9606)
Length
539 aa
Mass
58,487 Da
Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1) is an aldehyde dehydrogenase enzyme that catalyzes the conversion of L-aminoadipate-semialdehyde to L-2-aminoadipate in lysine catabolism. Beyond its role in amino acid metabolism, the protein mediates broad cytoprotective functions, including detoxification of lipid peroxidation-derived aldehydes, protection against oxidative stress and hyperosmotic stress, and inhibition of ferroptosis through membrane NADH generation and reactive aldehyde consumption (UniProt: P49419).
ALDH7A1 is primarily implicated in early-onset seizure disorders; biallelic mutations cause autosomal recessive epilepsy responsive to pyridoxine supplementation (UniProt: P49419). The protein's ferroptosis-suppressive activity and energy homeostasis regulation suggest broader roles in neuronal stress response.
In Alzheimer's Disease, ALDH7A1 shows ambiguous direction of change across subcellular fractions in post-mortem AD brain tissue compared to controls, with a mean log2 fold-change of −0.11 (Chaparral AD proteomics). This modest and inconsistent regulation across fractions suggests the protein's contribution to AD pathology is subtle or context-dependent rather than a major directional shift.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
⚠ Ambiguous — detected in AD samples, direction unclear across fractionsP3
-0.450
P2
not detected
S2
+0.239
S3
not detected
Mean log₂FC across detected fractions: -0.1056 (2 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
Aldehyde dehydrogenase enzyme that mediates important protective effects (PubMed:16491085, PubMed:20207735, PubMed:20554659, PubMed:21338592, PubMed:25554827, PubMed:31302938, PubMed:31652343, PubMed:38604394, PubMed:40233740). Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes (PubMed:16491085, PubMed:20207735, PubMed:21338592, PubMed:40233740). Involved in cellular defense against hyperosmotic stress by metabolizing betaine aldehyde to betaine, an important cellular osmolyte and methyl donor (PubMed:20207735)
Involved in lysine catabolism in the brain by mediating the conversion of L-aminoadipate-semialdehyde ((S)-2-amino-6-oxohexanoate) to L-2-aminoadipate
Acts as a key inhibitor of ferroptosis both by generating membrane NADH and decreasing the level of reactive aldehydes (PubMed:40233740). Recruited to plasma membrane in response to ferroptotic stress and phosphorylation by AMPK, generating membrane NADH to support AIFM2/FSP1 activity, an essential ferroptosis suppressor protein (PubMed:40233740). Also directly inhibits ferroptosis by decreasing lipid peroxidation via consumption of reactive aldehydes, such as 4-hydroxynonenal (4-HNE) and malonaldehyde (PubMed:40233740). Also acts as a regulator of cellular energy homeostasis in response to cellular energy stress, such as starvation and hypoxia, by inhibiting COPI-mediated intracellular transport, thereby reducing cellular energy consumption (PubMed:31492851)
Disease associations
Epilepsy, early-onset, 4, vitamin B6-dependentEPEO4
An autosomal recessive neurologic disorder ocharacterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride.
Sources
Last updated 5/8/2026, 6:34:20 AM