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The Role Of Heat Shock Protein 90 In The Keap1/Nrf2 Mediated Oxidative-Stress Response, Zheng Song
The Role Of Heat Shock Protein 90 In The Keap1/Nrf2 Mediated Oxidative-Stress Response, Zheng Song
Electronic Thesis and Dissertation Repository
Oxidative and proteotoxic stress are common hallmarks of Neurodegenerative diseases (NDs). Cellular proteostasis is maintained through Heat shock protein (Hsp) 90 and Stress-inducible protein 1 (STIP1) modulating the stability of their substrates (clients). Hsp90/heat shock factor (HSF)1 pathway activation attenuates proteotoxicity. Meanwhile, activating the Kelch-like ECH associated protein 1 (Keap1)/ nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway combats oxidative stress. Numerous studies attempted to individually manipulate the expression of Hsp90 or Nrf2 to treat NDs.
Novel interactions of Hsp90 with Nrf2 and Keap1 were discovered via yeast-2-hybrid screening (unpublished data). We analyzed their interactions through NMR spectroscopy, ITC, protein-binding assay, …