Olga Miller

Significance: Glutaredoxin (Grx1), an evolutionarily conserved and ubiquitous enzyme, regulates redox signal transduction and protein redox homeostasis by catalyzing reversible S-glutathionylation. Grx1 plays different roles in different cell types. In Parkinson's disease (PD), Grx1 regulates apoptosis signaling in dopaminergic neurons, so that lo...

Glutaredoxin (Grx1) is a ubiquitously expressed thiol-disulfide oxidoreductase that specifically catalyzes reduction of S-glutathionylated substrates. Grx1 is known to be a key regulator of pro-inflammatory signaling, and Grx1 silencing inhibits inflammation in inflammatory disease models. Therefore, we anticipate that inhibition of Grx1 could be a...

This supplementary table provides the list of proteins that were identified to be adducted by J02 to a detectable extent by mass spectrometry. The proteins are listed sequentially starting with those proteins displaying the highest fold-change in spectral counts in the J02 treated samples relative to the DMSO treated samples. (XLSX)

This supplementary figure provides the actual 1H NMR spectra for the J02 compound and its synthetic precursors. Descriptions of the NMR spectra are provided under Materials and Methods in the main text where the synthetic scheme (Fig 6) is described. (DOCX)

This supplementary figure provides the data showing that cytosolic Trx1 in BV2 cells is not inhibited by 40 μM J02, the concentration which inhibits Grx1 in the cells by 50%. (DOCX)

This supplementary figure provides the uncropped blots for Figs 3D and 5B, showing where the blots were cropped. (DOCX)

Aims: Neuroinflammation and redox dysfunction are recognized factors in Parkinson’s disease (PD) pathogenesis; and diabetes is implicated as a potentially predisposing condition. Remarkably, upregulation of glutaredoxin-1 (Grx1) is implicated in regulation of inflammatory responses in various disease contexts, including diabetes. Here we investigat...

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, caused by the degeneration of the dopaminergic neurons in the substantia nigra. Mutations in PARK7 (DJ-1) result in early onset autosomal recessive PD, and oxidative modification of DJ-1 has been reported to regulate the protective activity of DJ-1 in vitro. Glu...

Posttranslational modifications of cysteine sulfhydryl (-SH) moieties, e.g., S-nitrosylation, S-glutathionylation, or S-sulfuration, play an important role in cellular response to oxidative stress. Reversible cysteine modifications alter protein function and can play a critical role in redox signal transduction. Perturbation of sulfhydryl homeostas...

Motor activity of Caenorhabditis elegans is widely used to study the mechanisms ranging from basic neuronal functions to human neurodegenerative diseases. It may also serve as a paradigm to screen for potential therapeutic reagents treating these diseases. Here, we developed an automated, 96-well plate and liquid phase based system that quantifies...