Showing papers in "Current Opinion in Toxicology in 2016"

TL;DR: Small molecule activators of Nrf2 support mitochondrial integrity by promoting mitophagy and conferring resistance to oxidative stress-mediated permeability transition, with implications for stem cell self-renewal, cardiomyocyte regeneration, and neural stem/progenitor cell survival.

TL;DR: A molecular mechanism of Nrf2-activation by p62/SQSTM1 is delineated, and its physiological role as well as the pathophysiological significance in autophagy-knockout livers and human hepatocellular carcinoma is described.

TL;DR: In this review, several important and recent findings on epigenetic regulation and perspectives on Keap1-Nrf2 are discussed and shared.

TL;DR: Available and putative NRF2-targeted therapeutics are reviewed and their modes of action as well as their potential for disease prevention and treatment are discussed.

TL;DR: The molecular basis underlying the Keap1–Nrf2 function and drug discovery is described, which shows how ROS and electrophiles modify cysteine residues ofKeap1 to inactivate the ubiquitin E3 ligase activity of Keap 1, so that Nrf2 escapes from the KeAP1-mediated repression, migrates into the nucleus, and activates expression of its target genes.

TL;DR: Evidence supporting that hyperactivation of NRF2 is associated with tumor resistance to a variety of anticancer drugs through detoxification of drug- induced reactive oxygen species and electrophiles, preventing cellular accumulation of drugs, and inhibiting drug-induced apoptotic responses is discussed.

TL;DR: Although the human health implications of NRF2 dysregulation have been recognized for some time, a systems level view of this regulatory network is beginning to highlight keyNRF2-targeted AREs consistently associated with disease.

TL;DR: In this paper, biochemical and genetic evidence connecting NRF2 with neurodegenerative diseases was discussed, mainly in the context of preclinical mouse models and in patients with Alzheimer's and Parkinson's disease.

TL;DR: An overview of the role of Nrf2 in protection against drug and chemical toxicity, with a focus on the numerous in-vivo studies that have shown heightened sensitivity of NRF2 null (knockout) transgenic mice to such insults, is provided.

TL;DR: Nrf2-mediated antioxidant defense seems to play paradoxical Yin- and Yang-roles in regulating glucose homeostasis: while it protects insulin-responsive cells and β-cells from oxidative damage, it also blunts insulin- and glucose-triggered ROS signaling, resulting in insulin resistance and reduced insulin secretion.

TL;DR: Evidence is provided that Nrf2 is subject to repression by both Keap1 and the axis between GSK-3 and β-TrCP, which results in an increase in the levels of PIP3 produced by PI3K, and hence 3-phosphoinositide-dependent protein kinase-1 (PDK1) activity, which then stimulates PKB/Akt signaling.

TL;DR: A need to better understand the full scope of the NRF2 regulatory network is established because recent cancer genome sequencing efforts have uncovered a significant overrepresentation of somatic mutations that drive a sustainedNRF2 activation phenotype in cancer.

TL;DR: This evaluation illustrates the power of mass spectrometry-based protein sequencing to understand the signaling components and dynamics of the KEAP1–NRF2 pathway.

TL;DR: How whole-genome transcriptome analyses can identify the means through which Nrf2 transcriptionally modulates organ injury and morphology, cellular growth/proliferation, vasculature development, and immune response during BPD-like pathogenesis is described.

TL;DR: A short review of Keap1-Nrf2 protein–protein interaction inhibitors highlights structures from both classes and discusses their development, biological properties, and the future prospects for developing therapeutic agents.

TL;DR: How large-scale multi-omics cancer projects, such as The Cancer Genome Atlas (TCGA) have increased understanding of the mechanisms and consequences of NRF2 overactivity in cancer and how this information may impact cancer diagnostics and treatment in the future is discussed.

TL;DR: In this respect, the Silent Spring (1962) book as mentioned in this paper is considered as the landmark publication which changed the way of thinking about benefits and disadvantages of industrial evolution, and it was used as a warning that synthetic chemicals could also be a risk for human health and environment.