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
Tithi Roy,
Samuel T. Boateng,
Mohammad B. Uddin,
Sergette Banang-Mbeumi,
Rajesh K. Yadav,
Chelsea R. Bock,
Joy T. Folahan,
Xavier Siwe-Noundou,
Anthony L. Walker,
Judy A. King,
Claudia Buerger,
Shile Huang,
Jean Christopher Chamcheu
Affiliations
Tithi Roy
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
Samuel T. Boateng
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
Mohammad B. Uddin
Department of Toxicology and Cancer Biology, Center for Research on Environmental Diseases, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
Sergette Banang-Mbeumi
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
Rajesh K. Yadav
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
Chelsea R. Bock
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
Joy T. Folahan
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
Xavier Siwe-Noundou
Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, P.O. Box 218, Pretoria 0208, South Africa
Anthony L. Walker
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
Judy A. King
Department of Pathology and Translational Pathobiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
Claudia Buerger
Department of Dermatology, Venerology and Allergology, Clinic of the Goethe University, 60590 Frankfurt am Main, Germany
Shile Huang
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA
Jean Christopher Chamcheu
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA
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.
