The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds

Cells. 2023 Jun 20;12(12):1671. doi: 10.3390/cells12121671.


The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, and vitiligo, and is associated with poor treatment outcomes. Improved comprehension of the consequences of the dysregulated PI3K/Akt/mTOR pathway in patients with inflammatory dermatoses has resulted in the development of novel therapeutic approaches. Nonetheless, more studies are necessary to validate the regulatory role of this pathway and to create more effective preventive and treatment methods for a wide range of inflammatory skin diseases. Several studies have revealed that certain natural products and synthetic compounds can obstruct the expression/activity of PI3K/Akt/mTOR, underscoring their potential in managing common and persistent skin inflammatory disorders. This review summarizes recent advances in understanding the role of the activated PI3K/Akt/mTOR pathway and associated components in immune-mediated inflammatory dermatoses and discusses the potential of bioactive natural products, synthetic scaffolds, and biologic agents in their prevention and treatment. However, further research is necessary to validate the regulatory role of this pathway and develop more effective therapies for inflammatory skin disorders.

Keywords: PI3K-Akt-mTOR signaling pathway; acne; antioxidants, flavonoids and bioactive natural products/nutraceuticals; atopic dermatitis; biologics and targeted therapy; phytochemicals; psoriasis; skin inflammation; wound healing.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Dermatitis*
  • Humans
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Psoriasis* / drug therapy
  • Signal Transduction
  • Sirolimus
  • TOR Serine-Threonine Kinases / metabolism


  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Sirolimus
  • Biological Products