3BDO is a new mTOR activator which can also inhibit autophagy. It inhibited autophagy in human umbilical vein endothelial cells (HUVECs) and neuronal cells. 3BDO activated MTOR by targeting FKBP1A (FK506-binding protein 1A, 12 kDa). Activation of mTOR by 3BDO increased the phosphorylation of TIA1 (TIA1 cytotoxic granule-associated RNA binding protein/T-cell-restricted intracellular antigen-1)[1]. In vivo experiments confirmed that 3BDO activated mTOR and decreased the protein level of ATG13 in the plaque endothelium of apoE(-/-) mice. Importantly, 3BDO did not affect the activity of mTOR and autophagy in macrophage cell line RAW246.7 and vascular smooth muscle cells of apoE(-/-) mice, but suppressed plaque endothelial cell death and restricted atherosclerosis development in the mice. 3BDO protected VECs by activating mTOR and thus stabilized atherosclerotic lesions in apoE(-/-) mice[2]. 3BDO increased levels of insulin-degrading enzyme and neprilysin, suppressed autophagy via an mTOR pathway, lowered levels of Aβ, and prevented AD-like cognitive deficits in the AβPP/PS1 double transgenic mouse model[3].
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