The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration

Cell Signal. 2014 Dec;26(12):2694-701. doi: 10.1016/j.cellsig.2014.08.019. Epub 2014 Aug 28.


Disruption of autophagy plays an import role in neurodegenerative disorders, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates and survive. The kinase mammalian target of rapamycin (mTOR) is a major regulator of the autophagic process and is regulated by starvation, growth factors, and cellular stressors. Upstream of mTOR the survival PI3K/AKT pathway modulates mTOR activity that is also altered in neurodegenerative diseases of Alzheimer and Parkinson. Nevertheless, the interplay between the PI3K/AKT/mTOR pathway and the autophagic process is complex and a more detailed examination of tissue from patients suffering neurodegenerative diseases and of animal and cellular models is needed. In the present work we review the recent findings on the role of the PI3K/AKT/mTOR pathway in the modulation of the autophagic process in neuronal protection.

Keywords: Alzheimer's disease; Authophagy; Mammalian target of rapamycin complex; Neurodegeneration; Parkinson's disease; Phosphatidylinositol 3 kinase.

Publication types

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

MeSH terms

  • Animals
  • Autophagy / physiology
  • Humans
  • Neurodegenerative Diseases / metabolism*
  • Neurons / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Aggregates / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / metabolism*


  • Protein Aggregates
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases