The Mitochondria-Modulating Small Molecule TEM1657 Suppresses NFKBIZ Pathway and Resolves Th17-Driven Psoriatic Inflammation
Psoriasis is a chronic skin disease characterized by red, scaly plaques mainly driven by dysregulated T cells that induce keratinocytes (KCs) proliferation and inflammation. Despite significant advancements in disease management through biologics and topical therapies, these treatments offer only temporary relief and fail to prevent disease recurrence. Considering the current therapeutic needs,…
Psoriasis, a chronic skin condition, is characterized by red, scaly plaques and is primarily driven by dysregulated T cells that stimulate keratinocyte proliferation and inflammation. While biologics and topical therapies have provided temporary relief, they do not prevent disease recurrence. To address this need, researchers have developed a novel small molecule, TEM1657, derived from 3,5-dicaffeoylquinic acid.
TEM1657 has shown anti-inflammatory potency in psoriasis mouse models and Th17-stimulated keratinocyte cultures. The molecule modulates mitochondrial dynamics, specifically through OPA1, an inner mitochondrial membrane protein that regulates mitochondrial calcium influx and impacts cellular bioenergetics. Additionally, TEM1657 rapidly suppresses the transcription of NFKBIZ and various other psoriasis-associated genes, opening up a new therapeutic target for psoriasis and other NFKBIZ-related disorders.
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