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Mats Sandberg is Professor in Department med Biochemistry and Cell biology, University of Gothenburg, Sweden. His research involved the inducible anti-oxidant defense in brain.Brain cells are sensitive to oxidative stress, i.e. an imbalance between free radicals and the anti-oxidant systems. An intact defense system which can be up-regulated is vital for the survival of the brain in case of elevated oxidative stress. We are particularly interested in the inducible anti-oxidant systems mediated by the transcription factor Nrf2. Activation of Nrf2 by for example sub-toxic levels of free radicals and certain phytochemicals in vegetables leads to up-regulation of hundreds of protective genes. We have recently shown that activation of Nrf2 in astrocytes, the cells in the brain that supports neurons, can be down-regulated by inflammatory mediators. Such a down-regulation has been observed in the human hippocampus region of individuals suffering from Alzheimer’s disease. Our working hypothesis is that this down-regulation of Nrf2 can lead to neurodegeneration and memory dysfunction in Alzheimer’s disease. We have started to identify the molecular factors and the signaling behind the regulation of the Nrf2-system in cultured astrocytes. Activation of the kinases p38 and GSK3beta down-regulated whereas activation of ERK, JNK and Akt up-regulated the Nrf2-system. In addition, we observed that activation of histone-deacetylases by inflammatory mediators down-regulated the Nrf2-system. Activation of these enzymes has prolonged effects and regulates the expression of genes without changing the genetic code, so called epigenetic modification. We now study how stress hormone, certain environmental toxins and physical activity affect the Nrf2-system. We are particularly interested in epigenetic regulation of the Nrf2 system which we believe could down-regulate the anti-oxidant capacity in neurons, microglia and astrocytes in Alzheimer’s disease.
Basic Medicine, Neurosciences, Neurochemistry, Physiology, Cell and Molecular Biology, Immunology, Oncology