Details

Autor(en) / Beteiligte

• Oliveira, Júlia T.
• Dakic, Vanja
• Vitória, Gabriela
• Pedrosa, Carolina da S.G.
• Mendes, Mayara
• Aragão, Luiz Guilherme H.S.
• Cardim-Pires, Thyago R.
• Lelièvre, Damien
• Furtado, Daniel Rodrigues
• Pinheiro, Roberta O.
• Foguel, Débora
• Breton, Lionel
• Bouez, Charbel
• De Vecchi, Rodrigo
• Guimarães, Marília Zaluar P.
• Rehen, Stevens

Titel

Oligomeric α-Synuclein induces skin degeneration in reconstructed human epidermis

Ist Teil von

• Neurobiology of aging, 2022-05, Vol.113, p.108-117

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• •Reconstructed human epidermis (RHE) expresses α-Synuclein (α-Syn)•Oligomeric α-Synuclein (Oα-Syn) decreases proliferation in epidermal keratinocytes•Oα-Syn prompts NF-kB nuclear translocation in human epidermal keratinocytes•Oα-Syn increases the expression of IL-1β and TNF-α in RHE and the release of TNF-α•Cytokines inhibitors partially prevent the anti-proliferative effect of Oα-Syn 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 α-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 α-Synuclein (Oα-Syn) in 2D and 3D keratinocyte human models. Exogenous Oα-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. Oα-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1β and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1β inhibitor partially diminished RHE degeneration caused by Oα-Syn. These findings suggest that Oα-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging.