Alpha-aminoadipic semialdehyde dehydrogenase

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.