OAB-14, is a Bexarotene (HY-14171) derivative, 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 pathway in APP/PS1 transgenic mice[2].In Vivo: OAB-14 significantly alleviates cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice after administration for 15 days or 3 months. OAB-14 rapidly cleared 71% of Aβ by promoting microglia phagocytosis and increasing IDE and NEP expression. OAB-14 also attenuates the downstream pathological events of Aβ accumulation, such as synaptic degeneration, neuronal loss, tau hyperphosphorylation and neuroinflammation in APP/PS1 mice. OAB-14 has no significant effect on body weight or liver toxicity after acute and chronic treatment.
OAB-14 facilitates receptor-mediated endocytosis and restores autophagy flux via the AMPK/mTOR pathway. OAB-14 enhances the lysosomal activity, and reduced Aβ accumulation in lysosomes is observed in OAB-14-treated AD mice[2].