γ-crystallin Inhibitors

The chemical class of γ-crystallin inhibitors encompasses a variety of compounds that indirectly influence the stability, expression, or aggregation of γ-crystallin. These compounds target various cellular processes and signaling pathways that can indirectly impact the behavior of γ-crystallin in the eye lens. Notably, this class includes inhibitors of molecular chaperones like HSP90 (e.g., 17-AAG, Geldanamycin) and proteasome inhibitors (e.g., MG-132). The inhibition of these proteins and processes can lead to altered protein homeostasis, potentially affecting the stability and solubility of γ-crystallin, which is crucial for maintaining lens transparency.

Other compounds in this class target broader cellular stress responses or signaling pathways. For instance, autophagy inhibitors (e.g., 3-MA) and ER stress inducers (e.g., Tunicamycin) can disrupt cellular mechanisms responsible for protein quality control, while oxidative stress inducers (e.g., Paraquat) can lead to protein modifications and damage. Calcium channel blockers like Verapamil and protein kinase inhibitors such as Staurosporine indirectly modulate cellular signaling, which could have downstream effects on γ-crystallin. Additionally, compounds that induce DNA damage (e.g., Cisplatin) or disrupt mitochondrial function (e.g., Rotenone) could create a cellular environment that indirectly affects γ-crystallin's expression or stability.