Cell death in inflammatory neurodegeneration
We are investigating the roles of inflammation and mitochondria in cellular physiology and cell death, and in neurodegenerative and cardiovascular disease. Mitochondria have multiple roles in cell death. For example we find that mitochondria may regulate apoptosis by regulting the redox state of cytosolic cytochrome c. We have shown that NO regulates mitochondrial energy production in cells and cell death, and this may be important in many disease states.
In neurodegenerative, stroke, brain trauma or infection, brain astrocytes and microglial cells become inflammed and may kill surrounding neurons. We aim to understand the mechanisms of this inflammatory neurodegeneration, using both primary cultures and cell lines of neurons and glial cells, as well as animal models.
Techniques used include cell culture, electrodes, microscopy, spectroscopy, western blotting, molecular biology and biochemistry.
Brown GC, Borutaite V (2007) Mitochondrial regulation of caspase activation by cytochrome oxidase and tetramethylphenylenediamine (TMPD) via cytosolic cytochrome C redox state. J Biol Chem. 282, 31124-30.
Jekabsone, A., Nehrer, J., Borutaite, V. & Brown, G. C. (2007) Nitric oxide from neuronal nitric oxide synthase sensitises neurons to hypoxia-induced death via competitive inhibition of cytochrome oxidase. J. Neurochem. 103, 346-356.
Jekabsone A, Mander PK, Tickler A, Sharpe M, Brown GC. (2006) Fibrillar beta-amyloid peptide Abeta1-40 activates microglial proliferation via stimulating TNF-alpha release and H2O2 derived from NADPH oxidase: a cell culture study. J Neuroinflammation. 3:24.