Activation of mTOR: A culprit of Alzheimer’s disease?

Zhiyou Cai, Guanghui Chen, Wenbo He, Ming Xiao, Liang Jun Yan

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1015-1030
Number of pages16
JournalNeuropsychiatric Disease and Treatment
Volume11
DOIs
StatePublished - 9 Apr 2015

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Sirolimus
Alzheimer Disease
Autophagy
Glycogen Synthase Kinase 3
Amyloid Precursor Protein Secretases
Proto-Oncogene Proteins c-akt
Neurofibrillary Tangles
1-Phosphatidylinositol 4-Kinase
Amyloid beta-Protein Precursor
Amyloid Plaques
Somatomedins
Amyloid
Phosphorylation
Insulin
Pathology
Research

Keywords

  • Alzheimer’s disease
  • Mammalian target of rapamycin
  • Neurofibrillary tangles
  • Rapamycin
  • Signaling
  • β-amyloid

Cite this

Cai, Zhiyou ; Chen, Guanghui ; He, Wenbo ; Xiao, Ming ; Yan, Liang Jun. / Activation of mTOR : A culprit of Alzheimer’s disease?. In: Neuropsychiatric Disease and Treatment. 2015 ; Vol. 11. pp. 1015-1030.
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Activation of mTOR : A culprit of Alzheimer’s disease? / Cai, Zhiyou; Chen, Guanghui; He, Wenbo; Xiao, Ming; Yan, Liang Jun.

In: Neuropsychiatric Disease and Treatment, Vol. 11, 09.04.2015, p. 1015-1030.

Research output: Contribution to journalArticle

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