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

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.