Succinate-semialdehyde dehydrogenase, mitochondrial (ALDH5A1)

Succinate-semialdehyde dehydrogenase, mitochondrial (ALDH5A1), is an enzyme located in the mitochondria that catalyzes the oxidation of succinic semialdehyde to succinate in the "GABA shunt" pathway, thereby connecting neurotransmitter catabolism to the Krebs cycle for energy production. It is essential for the breakdown of the inhibitory neurotransmitter GABA; deficiency results in the accumulation of GABA and GHB, causing a rare autosomal recessive disorder characterized by intellectual disability, seizures, hypotonia, and autism spectrum features. Pathogenic variants in the ALDH5A1 gene disrupt enzyme function, impair mitochondrial energy metabolism, and increase cellular vulnerability to oxidative stress[1][2][3][4]. There are no approved direct pharmacological therapies, but enzyme stabilizers are under investigation as a potential therapeutic approach[4].

Other names

Aldehyde dehydrogenase 5 family member A1SSADHSSDHMitochondrial succinate semialdehyde dehydrogenaseNAD(+)-dependent succinic semialdehyde dehydrogenase

Pharmacological chaperones or folding enhancers (theoretical/experimental)[4], Supplementation strategies to bypass metabolic block (experimental)