The role of PI3K/AKT/FOXO signaling in psoriasis

Area of Science:

• Dermatology
• Molecular Biology
• Cell Signaling

Background:

• The Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway regulates cell proliferation and survival.
• Forkhead box O (FOXO) transcription factors inhibit cell proliferation and are negatively regulated by PI3K/AKT signaling.
• Psoriasis is a skin disease characterized by keratinocyte hyperproliferation, linked to PI3K/AKT pathway dysregulation and FOXO downregulation.

Purpose of the Study:

• To review the roles and mechanisms of PI3K and AKT in keratinocyte hyperproliferation.
• To examine the involvement of FOXO transcription factors in psoriasis.
• To identify PI3K/AKT/FOXO signaling and associated molecules as potential therapeutic targets for psoriasis.

Main Methods:

• Literature review of recent studies on PI3K/AKT/FOXO signaling in keratinocytes and psoriasis.
• Analysis of molecular mechanisms regulating keratinocyte proliferation in psoriasis.
• Investigation of upstream (e.g., PTEN) and downstream (e.g., mTOR) molecules in the PI3K/AKT pathway in psoriasis.

Main Results:

• PI3K/AKT signaling promotes keratinocyte proliferation by activating AKT and downregulating FOXO.
• Amplification of PI3K/AKT and loss of FOXO are observed in psoriatic lesions.
• Alterations in upstream (PTEN) and downstream (mTOR) regulators of PI3K/AKT signaling are common in psoriasis.

Conclusions:

• The PI3K/AKT/FOXO signaling axis plays a critical role in keratinocyte hyperproliferation in psoriasis.
• Dysregulation of this pathway, including upstream and downstream molecules, contributes to psoriasis pathogenesis.
• Targeting the PI3K/AKT/FOXO pathway offers a promising therapeutic strategy for psoriasis.