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mTOR 的活化： 阿尔茨海默氏症 (Alzheimer's disease) 的罪魁祸首？

 

Authors Cai Z, Chen G, He W, Xiao M, Yan LJ

Published Date April 2015 Volume 2015:11 Pages 1015—1030

DOI http://dx.doi.org/10.2147/NDT.S75717

Received 12 October 2014, Accepted 11 December 2014, Published 9 April 2015

Abstract: Alzheimer’s disease (AD) is characterized by cognitive impairment in clinical presentation, and by β-amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the mammalian target of rapamycin (mTOR) enhances Aβ generation and deposition by modulating amyloid precursor protein (APP) metabolism and upregulating β- and γ-secretases. mTOR, an inhibitor of autophagy, decreases Aβ clearance by scissoring autophagy function. mTOR regulates Aβ generation or Aβ clearance by regulating several key signaling pathways, including phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt), glycogen synthase kinase 3 [GSK-3], AMP-activated protein kinase (AMPK), and insulin/insulin-like growth factor 1 (IGF-1). The activation of mTOR is also a contributor to aberrant hyperphosphorylated tau. Rapamycin, the inhibitor of mTOR, may mitigate cognitive impairment and inhibit the pathologies associated with amyloid plaques and neurofibrillary tangles by promoting autophagy. Furthermore, the upstream and downstream components of mTOR signaling are involved in the pathogenesis and progression of AD. Hence, inhibiting the activation of mTOR may be an important therapeutic target for AD.
Keywords: Alzheimer’s disease, mammalian target of rapamycin, rapamycin, β-amyloid, neurofibrillary tangles, signalling






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