STCH激活剂

STCH activators can be broadly classified into two categories. The first category includes compounds that indirectly enhance STCH activity by disrupting the function of other heat shock proteins, specifically Hsp90. These compounds, such as Geldanamycin, 17-AAG, and Radicicol, are known to inhibit Hsp90, leading to the disruption of the Hsp90-Cdc37 chaperone complex. This disruption results in the compensatory activation of other heatshock proteins, including STCH, to maintain cellular homeostasis under stress conditions. Consequently, these compounds indirectly enhance STCH activity by triggering the heat shock response, a cellular defense mechanism against protein-damaging stressors. Puromycin falls into this category as well, as it induces the heat shock response, leading to the activation of various heat shock proteins including STCH.

The second category includes compounds that enhance STCH activity via their effects on autophagy. Autophagy is a cellular process that helps in maintaining cellular homeostasis by removing damaged organelles and proteins. Autophagy can be upregulated by inhibiting mTOR kinase, as seen with compounds such as AZD-8055, Torin 1, and Rapamycin. Upregulation of autophagy, in turn, enhances the activity of STCH, given its involvement in the autophagy-lysosome pathway. MG-132, a proteasome inhibitor, also enhances STCH activity by triggering a compensatory increase in autophagy upon proteasome inhibition. Bafilomycin A1 and Chloroquine, both disruptors of lysosomal acidification, indirectly enhance STCH activity by causing an upregulation of autophagy. Lastly, 3-MA and Spautin-1, despite being autophagy inhibitors, can also enhance STCH activity indirectly by disrupting autophagic flux and causing a compensatory upregulation of other elements in the pathway.