Novel Hsp90 inhibitors reduce high-molecular-mass oligomeric αsyn species. Western blots of S1- and S2-transfected H4 cells treated with various Hsp90 inhibitors. A, composite native and denatured PAGE of pretreatment with Hsp90 inhibitors. Blots were probed for αsyn (native and denatured), Hsp70 (denatured only), and GAPDH (denatured only). A reduction in higher-molecular-mass and monomeric αsyn species with a concomitant 6- to 8-fold up-regulation in Hsp70 after pretreatment with Hsp90 inhibitors was observed. B, composite native and denatured PAGE of cotreatment with Hsp90 inhibitors. Blots were probed for αsyn (native and denatured), Hsp70 (denatured only), and GAPDH (denatured only). Cotreatment resulted in some reduction in higher-molecular-mass species (SNX-8891, SNX-3113, and SNX-0723) as well as an apparent redistribution of αsyn species from higher-molecular-mass to monomeric (SNX-3113) with a concomitant 2- to 3-fold up-regulation in Hsp70 after Hsp90 inhibition. Representative blots from n = 3 of each condition.