mTOR: on target for novel therapeutic strategies in the nervous system

Trends Mol Med. 2013 Jan;19(1):51-60. doi: 10.1016/j.molmed.2012.11.001. Epub 2012 Dec 19.

Abstract

The mammalian target of rapamycin (mTOR), the key component of the protein complexes mTORC1 and mTORC2, plays a critical role in cellular development, tissue regeneration, and repair. mTOR signaling can govern not only stem cell development and quiescence but also cell death during apoptosis or autophagy. Recent studies highlight the importance of both traditional and newly recognized interactors of mTOR, such as p70S6K, 4EBP1, GSK-3β, REDD1/RTP801, TSC1/TSC2, growth factors, wingless, and forkhead transcription factors, that influence Alzheimer's disease, Parkinson's disease, Huntington's disease, tuberous sclerosis, and epilepsy. Targeting mTOR in the nervous system can offer exciting new avenues of drug discovery, but crucial to this premise is elucidating the complexity of mTOR signaling for robust and safe clinical outcomes.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Humans
  • Nervous System / drug effects
  • Nervous System / metabolism*
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism*
  • Oxidative Stress
  • Phosphorylation
  • Protein Interaction Domains and Motifs
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / chemistry
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases