Targeting the mTOR signaling network for Alzheimer's disease therapy

Mol Neurobiol. 2014 Feb;49(1):120-35. doi: 10.1007/s12035-013-8505-8. Epub 2013 Jul 14.

Abstract

The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that can sense environmental stimuli such as growth factors, energy state, and nutrients. It is essential for cell growth, proliferation, and metabolism, but dysregulation of mTOR signaling pathway is also associated with a number of human diseases. Encouraging data from experiments have provided sufficient evidence for the relationship between the mTOR signaling pathway and Alzheimer's disease (AD). Upregulation of mTOR signaling pathway is thought to play an important role in major pathological processes of AD. The mTOR inhibitors such as rapamycin have been proven to ameliorate the AD-like pathology and cognitive deficits effectively in a broad range of animal models. Application of mTOR inhibitors indicates the potential value of reducing mTOR activity as an innovative therapeutic strategy for AD. In this review, we will focus on the recent process in understanding mTOR signaling pathway and the vital involvement of this signaling pathway in the pathology of AD, and discuss the application of mTOR inhibitors as potential therapeutic agents for the treatment of AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Animals
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Humans
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sirolimus / administration & dosage
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism*
  • TOR Serine-Threonine Kinases / physiology

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus