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bioRxiv · 10.64898/2026.10.08.757342

A metabolic perspective on eIF1A and eIF3B inhibition as a potential therapeutic strategy in psoriasis

Bordag, N.·Bourgeois, B. M. R.·Madl, T.·Wolf, P.·Golob-Schwarzl, N.
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Abstract

Psoriasis is a chronic inflammatory skin disease marked by epidermal hyperplasia and distinct metabolic alterations. Here, we investigated the metabolic impact of targeting translation initiation factors by performing 1H NMR-based metabolomic profiling on polar skin extracts from imiquimod-induced (IMQ) and K5.TGF{beta}1 transgenic (TGF{beta}) mouse models treated with eIF1A or eIF3B siRNA. IMQ-treated skin demonstrated significant, human-like metabolic shifts, including depleted energy substrates (glucose, glycogen, 3-hydroxybutyrate) and elevated phospholipid/nucleotide markers, which correlated strongly with epidermal thickness. In contrast, TGF{beta} skin exhibited no broad baseline polar metabolome changes. eIF1A/eIF3B inhibition selectively attenuated IMQ-associated energy and phospholipid alterations without causing widespread metabolic disruption in TGF{beta} skin. Overall, eIF1A/eIF3B inhibition ameliorated psoriasis-like pathology and mitigated disease-associated metabolic demands in a context-dependent manner.

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Bordag, N., Bourgeois, B. M. R., Madl, T., Wolf, P., Golob-Schwarzl, N.. 2026-10-15. A metabolic perspective on eIF1A and eIF3B inhibition as a potential therapeutic strategy in psoriasis. https://doi.org/10.64898/2026.10.08.757342

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