Figure 6.

PI3K/Akt pathway and its relationship with skin disorders/diseases. IGF-1 and GPCR are the first step, followed by the activation of the classical PIP3 pathway to activate AKT; the PTEN regulatory molecule is activated by PIP3 and can be dephosphorylated to pass to PIP2 and decrease the action of this pathway; therefore, if PTEN is inactivated a sustained activation of PI3K/Akt could be achieved. In turn, if AKT was activated, it could activate mTORC1 resulting in cell growth and proliferation. Another effect was to phosphorylate TSC2 by inhibiting it for its subsequent activation of mTORC1 indirectly through Rheb-GTP. Indirectly, the activation of this pathway could increase the expression of MMP-2, whose function is the degradation of the extracellular matrix and favors metastasis. FOXO is a protein downstream of this pathway; it is a mediator of non-malignant skin disorders, responsible for the control of the cell cycle, apoptosis, longevity, and healing, and involved in the inhibition of lipogenesis. This protein can give rise to disorders such as acne, psoriasis and promote the apoptosis of keratinocytes. AGA: Androgenic alopecia; AKT: protein kinase B; FoxO1: Forkhead box O1; GPCR: G-protein-coupled receptors; GSK3: glycogen synthase kinase 3; IGF-1: Insulin-like growth factor 1; IKK: IkB-kinase; IRS-1/2: insulin receptor substrate-1/2; MAD1: MAX dimerization protein 1; MDM2: murine double minute 2; MLK3: mixed lineage kinase 3; mTORC1/2: mTOR complex 1/2; PDK1: phosphoinositide-dependent protein kinase 1; PI3K: phosphatidylinositol 3-kinase; PIP2: phosphatidylinositol 4,5-biphosphate; PIP3: phosphatidylinositol 3,4,5-triphosphate; PTEN: Phosphatase and tensin homologue; RTK: receptor tyrosine kinases; SREBP: sterol regulatory element-binding proteins; TSC1/2: tuberous sclerosis complex 1/2. Created with BioRender.com (accessed on 2 June 2023).