The three genes associated with chronic kidney disease (AGT GLO1 and SHROOM3) showed associations with both the high levels of oxidatively damaged DNA and genomic instability.
The most active compound (ST018515) showed an IC50 of 0.34 +/- 0.03 muM which compared to reported GLO-I inhibitors can be considered a potent inhibitor making it a good candidate for further optimization towards designing more potent GLO-I inhibitors.
Results indicate that the GLO1 loss of function (GLO1 (fs) mutation derived from the schizophrenia patient and the engineered GLO1 (-/-) mutation) impaired the cellular development of iPS cells because of the enhanced carbonyl stress.
The schizophrenia case with the highest neurite curvature carried a frame shift mutation in the GLO1 gene suggesting that oxidative stress due to the GLO1 mutation caused the structural alteration of the neurites.
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