ArticleJID innovations : skin science from molecules to population health2026
Distinct and shared effects of individual γ-secretase inhibitors on human keratinocytes.
Article in JID innovations : skin science from molecules to population health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Gamma secretase (γ-secretase) is an enzymatic transmembrane complex responsible for the cleavage of over 100 substrates, including notch, E-cadherin, amyloid precursor protein, specific cytokine receptors, and other type I transmembrane proteins. Genetic variants in the γ-secretase complex are associated with familial hidradenitis suppurativa (HS), where they are predicted to inactivate enzymatic function. Further, γ-secretase inhibitors cause HS-like pathologies in patients with desmoid tumors. However, it is unclear how modulation of γ-secretase activity in keratinocytes impacts cellular processes and contributes to HS pathophysiology. We explored how the loss of γ-secretase function impacts keratinocyte-mediated inflammatory cytokine and chemokine production and adhesion, two key keratinocyte processes altered in HS. We used pharmacological inhibitors of γ-secretase (SCP0004, nirogacestat, and E2012) that have different mechanisms of action and substrate selectivity (eg
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