Terazosin activates Pgk1 and Hsp90 to promote stress resistance

摘要: Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered terazosin (TZ), a widely marketed α1-adrenergic receptor antagonist, alleviated improved survival in rodent models of stroke sepsis. Through combined studies enzymology X-ray crystallography, we TZ binds new target, phosphoglycerate kinase 1 (Pgk1), activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the generated Pgk1 may enhance chaperone activity Hsp90, an ATPase known associate with Upon activation, Hsp90 promotes multistress resistance. Our demonstrate has protein Pgk1, reveal corresponding biological effect. As clinical drug, be quickly translated into treatments including