Oligomeric a-Synuclein induces skin degeneration in reconstructed human epidermis

Aged and photoaged skin exhibit fine wrinkles that are signs of epidermal inflammation and degeneration. It has been shown that healthy elderly skin expresses amyloidogenic proteins, including alpha-Synuclein, which are known to oligomerize and trigger inflammation and neurodegeneration. However, little is known about their putative role in skin physiology and sensitivity. To unravel this possible role, we investigated the impact of oligomeric alpha-Synuclein (O alpha-Syn) in 2D and 3D keratinocyte human models. Exogenous O alpha-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. O alpha-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1 beta and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1 beta inhibitor partially diminished RHE degeneration caused by O alpha-Syn. These findings suggest that O alpha-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging. (C)(& nbsp;2022 The Authors. Published by Elsevier Inc.

Automated summary

This study reveals that oligomeric alpha-Synuclein (O alpha-Syn) induces inflammation and degeneration in the skin, leading to a decrease in keratinocyte proliferation and thickness of the epidermis. These findings shed light on the potential role of O alpha-Syn in the aging process of the skin.