Chemical biology of retina-protective electrophilic compounds

2015 Fiscal Year Final Research Report

• Project/Area Number: 25350985
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Tokyo University of Technology (2014-2015); Iwate University (2013)
• Principal Investigator: SATOH Takumi 東京工科大学, 応用生物学部, 教授 (10300831)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Nrf2 / HSF-1 / Keap1 / HSP90 / Electrophile / Neuronal death / Oxidative stress / Retina

Outline of Final Research Achievements

Keap1/Nrf2 and HSP90/HSF-1 pathways play a central role in combatting cellular oxidative damage and related endoplasmic reticulum stress. Electrophilic compounds have been shown to be activators of these transcription-mediated responses. We hypothesized that the para-hydroquinone moiety was critical for this activation because it enhanced transcription of these neuroprotective pathways to a greater degree than that of the corresponding ortho-hydroquinone isomer. This notion was based on the differential oxidation potentials of the isomers for the transformation of the hydroquinone to the active, electrophilic quinone species. Here, to further test this hypothesis, we synthesized a pair of para- and ortho-hydroquinone-based proelectrophilic compounds and measured their redox potentials using analytical cyclic voltammetry. The redox potential was then compared with functional biological activity, and the para-hydroquinones demonstrated a superior neuroprotective profile.

Free Research Field

神経科学