Phytochemical modulation of the Akt/mTOR pathway and its potential use in cutaneous disease

Arch Dermatol Res. 2014 Dec;306(10):861-71. doi: 10.1007/s00403-014-1480-8. Epub 2014 Jun 28.

Abstract

The mechanistic target of rapamycin (mTOR) is involved in the regulation of cellular growth, proliferation, lipid synthesis, and protein translation. The mTOR pathway involves two complexes: the mechanistic target of rapamycin complex 1 (mTORC1) and the mechanistic target of rapamycin complex 2 (mTORC2). Both mTOR complexes have been implicated in the development and progression of various skin diseases including melanoma, psoriasis, and acne vulgaris. Here, we review the role of both mTORC1 and mTORC2 as well as their upstream modulators, phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), and their downstream targets in various dermatologic diseases. Phytochemicals, plant-derived naturally occurring compounds, have been shown to regulate the mTOR pathway and may serve as novel therapeutic agents in dermatological disease. Here, we review phytochemicals in the context of the mTOR pathway and their potential use in cutaneous disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Dermatologic Agents / therapeutic use*
  • Enzyme Activation
  • Enzyme Activators / therapeutic use*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Molecular Targeted Therapy
  • Multiprotein Complexes / antagonists & inhibitors
  • Multiprotein Complexes / metabolism
  • Phosphorylation
  • Plant Extracts / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Skin / drug effects*
  • Skin / enzymology
  • Skin / pathology
  • Skin Diseases / diagnosis
  • Skin Diseases / drug therapy*
  • Skin Diseases / enzymology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Dermatologic Agents
  • Enzyme Activators
  • Multiprotein Complexes
  • Plant Extracts
  • Protein Kinase Inhibitors
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases