Dr Guy Brown
Dr Guy Brown is pleased to consider applications from prospective PhD students.
http://www.guybrown.net (personal home page)
We are interested in the mechanisms of inflammatory neurodegeneration in the brain. We have been using cultures of neurons and glia to investigate how microglia become activated by inflammatory stimuli (such as cytokines, LPS, LTA, prions and beta-amyloid) and how such microglia damage neurons. We are particularly interested in nitric oxide, oxidants, glutamate, hypoxia, mitochondria, apoptosis, phagocytosis and interactions between neurons and glia. We have shown: how NO kills neurons, how the microglial NADPH oxidase regulates inflammation, how Ab and prions activate microglia, how hypoxia interacts with NO, how the proliferation of microglia and neuronal precursors is regulated by NO and oxidants, and how mitochondria contribute to neuronal death. We are also interested in the regulation of apoptosis and its interaction with phagocytosis. The mechanisms of phagocytosis in the brain, and their roles in brain pathologies are current preoccupations.
Traumatic brain injury
Chris Cooper Web: http://www.essex.ac.uk/bs/staf...
Simon Heales Web: http://www.ion.ucl.ac.uk/neuroch...
Salvador Moncada Web: http://www.ucl.ac.uk/wibr/re...
Emilio Clementi Web: http://www.fondazionesanraffaele.it/Home/Ri...
Borutaite V, Brown GC (2007), “Mitochondrial regulation of caspase activation by cytochrome oxidase and tetramethylphenylenediamine via cytosolic cytochrome c redox state.” J Biol Chem 282(43):31124-30 Details
Jekabsone A, Neher JJ, Borutaite V, Brown GC (2007), “Nitric oxide from neuronal nitric oxide synthase sensitises neurons to hypoxia-induced death via competitive inhibition of cytochrome oxidase.” J Neurochem 103(1):346-56 Details
Jekabsone A, Mander PK, Tickler A, Sharpe M, Brown GC (2006), “Fibrillar beta-amyloid peptide Ab1-40 activates microglial proliferation via stimulating TNF-b release and H2O2 derived from NADPH oxidase: a cell culture study” J Neuroinflam 3:24 Details
Fricker M, Neher JJ, Zhao JW, Théry C, Tolkovsky AM, Brown GC (2012), “MFG-E8 Mediates Primary Phagocytosis of Viable Neurons during Neuroinflammation.” J Neurosci 32(8):2657-66 Details
Brown GC, Borutaite V (2011), “There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells.” Mitochondrion Details
Neher JJ, Neniskyte U, Zhao JW, Bal-Price A, Tolkovsky AM, Brown GC (2011), “Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death.” J Immunol 186(8):4973-83 Details
Neniskyte U, Neher JJ, Brown GC (2011), “Neuronal death induced by nanomolar amyloid β is mediated by primary phagocytosis of neurons by microglia.” J Biol Chem 286(46):39904-13 Details
Brown GC (2010), “The principle of sufficiency and the evolution of control: using control analysis to understand the design principles of biological systems.” Biochem Soc Trans 38(5):1210-4 Details
Brown GC (2010), “Nitric oxide and neuronal death.” Nitric Oxide 23(3):153-65 Details
Brown GC, Neher JJ (2010), “Inflammatory neurodegeneration and mechanisms of microglial killing of neurons.” Mol Neurobiol 41(2-3):242-7 Details
Brown RD, Burke GA, Brown GC (2009), “Dependence of leukemic cell proliferation and survival on H2O2 and L-arginine.” Free Radic Biol Med 46(8):1211-20 Details
Thompson AJ, Mander PK, Brown GC (2009), “The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide.” Br J Pharmacol 158(5):1338-43 Details
Brown GC, Borutaite V (2008), “Regulation of apoptosis by the redox state of cytochrome c.” Biochim Biophys Acta 1777(7-8):877-81 Details
Brown GC (2007), “Mechanisms of inflammatory neurodegeneration: iNOS and NADPH oxidase.” Biochem Soc Trans 35(Pt 5):1119-21 Details
Neher JJ, Brown GC (2007), “Neurodegeneration in models of Gram-positive bacterial infections of the central nervous system.” Biochem Soc Trans 35(Pt 5):1166-7 Details
Bal-Price A, Gartlon J, Brown GC (2006), “Nitric oxide stimulates PC12 cell proliferation via cGMP and inhibits at higher concentrations mainly via energy depletion.” Nitric Oxide 14(3):238-46 Details
Borutaite V, Brown GC (2006), “S-nitrosothiol inhibition of mitochondrial complex I causes a reversible increase in mitochondrial hydrogen peroxide production.” Biochim Biophys Acta 1757(5-6):562-6 Details
Mander PK, Jekabsone A, Brown GC (2006), “Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase.” J Immunol 176(2):1046-52 Details
Mander P, Borutaite V, Moncada S, Brown GC (2005), “Nitric oxide from inflammatory-activated glia synergizes with hypoxia to induce neuronal death.” J Neurosci Res 79(1-2):208-15 Details
Mander P, Brown GC (2005), “Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration.” J Neuroinflammation 2:20 Details
Brown GC, Borutaite V (2004), “Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols.” Biochim Biophys Acta 1658(1-2):44-9 Details
Mander P, Brown GC (2004), “Nitric oxide, hypoxia and brain inflammation.” Biochem Soc Trans 32(Pt 6):1068-9 Details
Yung HW, Bal-Price AK, Brown GC, Tolkovsky AM (2004), “Nitric oxide-induced cell death of cerebrocortical murine astrocytes is mediated through p53- and Bax-dependent pathways.” J Neurochem 89(4):812-21 Details
Brown GC, Bal-Price A (2003), “Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria.” Mol Neurobiol 27(3):325-55 Details
Bal-Price A, Matthias A, Brown GC (2002), “Stimulation of the NADPH oxidase in activated rat microglia removes nitric oxide but induces peroxynitrite production.” J Neurochem 80(1):73-80 Details
Bal-Price A, Moneer Z, Brown GC (2002), “Nitric oxide induces rapid, calcium-dependent release of vesicular glutamate and ATP from cultured rat astrocytes.” Glia 40(3):312-23 Details
Golde S, Chandran S, Brown GC, Compston A (2002), “Different pathways for iNOS-mediated toxicity in vitro dependent on neuronal maturation and NMDA receptor expression.” J Neurochem 82(2):269-82 Details
Bal-Price A, Brown GC (2001), “Inflammatory neurodegeneration mediated by nitric oxide from activated glia, inhibiting neuronal respiration, causing glutamate release and excitoxicity” J Neuroscience 21:6480-6491
Bal-Price A, Brown GC (2001), “Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity.” J Neurosci 21(17):6480-91 Details