Chemical Probe To Monitor the Parkinsonism-Associated Protein DJ-1 in Live Cells

ACS Chemical Biology
Jonas DrechselStephan A Sieber

Abstract

Reactive oxygen species (ROS) play an important role in the onset of Parkinson's disease (PD), and deciphering protective mechanisms is a major goal for therapeutic development. Here, DJ-1 (PARK7) gained major attention when a conserved cysteine residue with a putative role in oxidative stress sensing/protection was linked to PD. Inspired by previous studies with a bacterial homologue of DJ-1, several amino-epoxycylcohexenones were screened for enzyme inhibition, and a chemical probe with specificity for the human ortholog was selected for cellular studies. The probe selectively labeled the cysteine oxidation sensor and whole proteome analysis in HeLa, A549, and SHSY5Y cell lines confirmed strong enrichment of reduced DJ-1 as the most prominent target. Increasing levels of oxidative stress diminished this signal demonstrating the utility of our tool compound for selective in situ monitoring of this important biomarker in its reduced state.

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Citations

Jul 6, 2019·Journal of Synchrotron Radiation·Henry van den Bedem, Mark A Wilson
Sep 6, 2019·Journal of Clinical Medicine·Mariaelena Repici, Flaviano Giorgini
Dec 8, 2020·Chemical Society Reviews·Liqian GaoShao Q Yao
May 10, 2021·Trends in Biochemical Sciences·Igor Maksimovic, Yael David
Jul 7, 2021·Biochemistry. Biokhimii︠a︡·Olga A Buneeva, Alexey E Medvedev
Aug 7, 2021·RSC Medicinal Chemistry·Igor MaksimovicYael David
Aug 1, 2018·ACS Chemical Biology·Shinya TashiroKouhei Tsumoto

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