megalin Activators

Megalin, a multifunctional endocytic receptor predominantly expressed in renal proximal tubule cells, plays a crucial role in the reabsorption of filtered proteins. The identified chemicals presented here, albeit not proven direct activators, modulate megalin activity through intricate cellular pathways. Gossypol, a natural compound, indirectly activates megalin by impacting the PI3K/AKT pathway, which regulates megalin expression and function in specific cellular contexts. Resveratrol, a polyphenol, indirectly activates megalin through its influence on SIRT1 activity, affecting pathways linked to megalin expression and trafficking. Sulforaphane, found in cruciferous vegetables, activates NRF2, indirectly promoting megalin expression by modulating cellular redox status and enhancing endocytic capacity. AICAR, an AMPK activator, indirectly activates megalin by modulating AMPK-dependent pathways, impacting megalin expression and trafficking in response to altered energy status.

Troglitazone, a PPARγ agonist, indirectly activates megalin by influencing PPARγ-dependent pathways, altering megalin expression and function transcriptionally. Raloxifene, a selective estrogen receptor modulator, indirectly activates megalin by modulating estrogen receptor signaling, impacting megalin expression and function in a hormone-dependent manner. Dasatinib, a tyrosine kinase inhibitor, indirectly activates megalin through its effects on Src family kinases, influencing megalin expression and function kinase-dependently. Parthenolide, found in feverfew, indirectly activates megalin by modulating NF-κB signaling, impacting megalin expression and function through altered transcriptional regulation. GW501516, a PPARδ agonist, indirectly activates megalin by influencing PPARδ-dependent pathways, altering megalin expression and function transcriptionally. Betulinic acid, a natural compound, indirectly activates megalin through its effects on the STAT3 pathway, influencing megalin expression and function transcriptionally. C646, a p300/CBP inhibitor, indirectly activates megalin by affecting histone acetylation, influencing megalin expression and function epigenetically. In conclusion, while direct megalin activators remain elusive, these chemicals show promise in influencing megalin activity through intricate cellular pathways, providing a foundation for further exploration into their regulatory roles in megalin-mediated endocytosis.