β-Amyloid regulates leptin expression and tau phosphorylation through the mTORC1 signaling pathway.

摘要: J. Neurochem. (2010) 115, 373–384. Abstract High levels of the adipocytokine leptin are associated with reduced risk Alzheimer’s disease. Leptin treatment also reduces β-amyloid (Aβ) in vivo and vitro models Aβ interact Akt/mammalian target rapamycin complex 1 (mTORC1) signaling pathway. Akt/mTORC1 activation tau phosphorylation through inhibition downstream enzyme GSK-3β. mTORC1 regulates translation many proteins including leptin. While has been shown to inactivate Akt, inhibit mTORC1, facilitate tau, activates both Akt phosphorylation. However, extent which may modulate expression increase involving not determined. In this study, we show that incubation organotypic slices from rabbit hippocampus down-regulates expression, inhibits GSK-3β, increases phosphorylation, inactivates mTORC1. reverses effects by alleviating inhibition, preventing GSK-3β activation, reducing activating On other hand, Rapamycin, an allosteric inhibitor does affect Our results demonstrate for first time