Amyloid-beta–Amyloid-beta binding alcohol dehydrogenase protein-protein interface (Aβ-ABAD interface)

The Amyloid-beta–Amyloid-beta binding alcohol dehydrogenase (Aβ-ABAD) protein-protein interface is a significant therapeutic target in Alzheimer's disease research. ABAD, also known as 17β-hydroxysteroid dehydrogenase type 10 (HSD17B10), is a multifunctional mitochondrial enzyme involved in the metabolism of steroids, fatty acids, and isoleucine (UniProt P56537). In the brains of Alzheimer's patients, Aβ peptide translocates into the mitochondria and binds directly to ABAD, which inhibits the enzyme's normal protective functions and triggers mitochondrial dysfunction (Lustbader et al., 2004, Science). This interaction leads to increased oxidative stress, impaired energy metabolism, and eventually neuronal apoptosis (Yan et al., 2007, Journal of Neuroscience). Therapeutic strategies focus on developing small molecules or decoy peptides that can disrupt this specific protein-protein interaction without interfering with the enzyme's vital metabolic activities (Yao et al., 2011, Journal of Alzheimer's Disease). By preventing Aβ from binding to ABAD, these agents aim to preserve mitochondrial integrity and protect neurons from Aβ-induced toxicity. Small molecule inhibitors like AG18051 have demonstrated the ability to block this interaction and reduce mitochondrial stress in experimental models. However, a major challenge remains in ensuring that inhibitors do not disrupt the essential metabolic roles of the ABAD enzyme itself.

Other names

Amyloid-beta–HSD17B10 interfaceAβ-ABAD complexAmyloid-beta–ERAB interfaceAβ-HSD10 interaction

Inhibition of the protein-protein interaction between Amyloid-beta and ABAD to prevent mitochondrial dysfunction and oxidative stress.