17-AAG (17-allylamino-17-demethoxygeldanamycin) is a potent inhibitor of heat shock protein 90 (HSP90), a molecular chaperone essential for the stability and function of numerous client proteins involved in cell signaling, survival, and protein homeostasis. Originally developed as an anticancer agent due to its selective affinity for tumor-derived HSP90, 17-AAG has gained attention in neuroscience for its ability to modulate protein degradation pathways. Notably, 17-AAG induces autophagy, a cellular clearance mechanism critical for the removal of misfolded proteins such as alpha-synuclein-an aggregation-prone protein implicated in Parkinson's disease and other synucleinopathies. By promoting autophagic flux, 17-AAG may help restore proteostasis in neural cells and reduce neurotoxicity associated with protein aggregation. Its dual role in inhibiting Akt signaling and enhancing protein clearance positions 17-AAG as a promising candidate for therapeutic exploration in neurodegenerative disorders characterized by proteotoxic stress.
