OAB-14, is a Bexarotene 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[1][2].
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[1].
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].
[1]. Guo X, et al. OAB-14 Effectively Ameliorates the Dysfunction of the Endosomal-Autophagic-Lysosomal Pathway in APP/PS1 Transgenic Mice. ACS Chem Neurosci. 2021;12(21):3985-3993.
[2]. Yuan C, et al. OAB-14, a bexarotene derivative, improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. Biochim Biophys Acta Mol Basis Dis. 2019;1865(1):161-180.