Gosset Amyloid beta-binding alcohol dehydrogenase Overview
Amyloid beta-binding alcohol dehydrogenase is a mitochondrial enzyme belonging to the short-chain dehydrogenase/reductase family. It is also known as 17β-hydroxysteroid dehydrogenase type 10. This enzyme has a broad substrate specificity, including roles in steroid metabolism and energy regulation within mitochondria. Critically, it binds amyloid-beta peptide with high affinity; this interaction exacerbates amyloid-beta-induced oxidative stress, impairs mitochondrial function, and contributes to neuronal dysfunction observed in Alzheimer's disease. Inhibition of the ABAD–amyloid-beta interaction—using small molecules or decoy peptides—has been shown to protect against these pathological effects in preclinical models by improving mitochondrial activity, reducing oxidative damage, enhancing degradation of amyloid-beta within mitochondria, and improving cognitive performance. As such, ABAD represents an emerging therapeutic target for neurodegenerative diseases characterized by amyloid pathology.
Mechanism of Action
Inhibitors block the interaction between ABAD and amyloid-beta, reducing mitochondrial dysfunction and neuronal toxicity associated with Alzheimer’s disease.
Biological Functions
Disease Associations
Safety Considerations
- Targeting mitochondrial enzymes can potentially disrupt essential cellular energy processes.
Interacting Drugs
Associated Biomarkers
| Biomarker |
|---|
| Elevated levels of ABAD in cerebral cortex and hippocampus in Alzheimer’s disease models/brains may serve as a biomarker for AD progression or therapeutic response |