Targeting PRAS40 for multiple diseases

Drug Discov Today. 2016 Aug;21(8):1222-31. doi: 10.1016/j.drudis.2016.04.005. Epub 2016 Apr 13.


Proline-rich Akt substrate 40kDa (PRAS40) bridges cell signaling between protein kinase B (Akt) and the mammalian target of rapamycin complex 1 (mTORC1). Both Akt and mTORC1 can phosphorylate PRAS40. As a negative regulator of mTORC1, PRAS40 prevents the binding of mTOR to its substrates. The phosphorylation of PRAS40 results in its dissociation from mTORC1 and enhanced mTOR activation. PRAS40 in conjunction with mTORC1 has been closely associated with programmed cell death and is implicated in diabetes mellitus (DM), cardiovascular diseases, cancer, and neurological diseases. Thus, targeting PRAS40 might hold great promise for innovative therapeutic strategies for these diseases.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis
  • Autophagy
  • Cardiovascular Diseases / metabolism*
  • Diabetes Mellitus / metabolism*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Neoplasms / metabolism*
  • Nervous System Diseases / metabolism*
  • Oxidative Stress


  • AKT1S1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Mechanistic Target of Rapamycin Complex 1