OAB-14 is a Bexarotene derivative that improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. OAB-14 effectively ameliorates the dysfunction of the endosomal-autophagic-lysosomal(EAL) pathway in APP/PS1 transgenic mice [1] [2].

OAB-14 significantly improves cognitive function in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice when administered for either 15 days or 3 months, by promoting microglia phagocytosis, enhancing IDE and NEP levels, and reducing Aβ by 71%. This compound mitigates Aβ-induced pathological outcomes, including synaptic degeneration, neuronal loss, tau hyperphosphorylation, and neuroinflammation, without adversely affecting body weight or causing liver toxicity, even after prolonged use. Furthermore, OAB-14 boosts receptor-mediated endocytosis and normalizes autophagy flux through the AMPK/mTOR pathway, increasing lysosomal activity and decreasing Aβ accumulation in lysosomes of treated AD mice.