Professor Guy Brown

Guy Brown

University position

Professor

Professor Guy Brown is pleased to consider applications from prospective PhD students.

Departments

Department of Biochemistry

Email

gcb3@cam.ac.uk

Home page

http://www.guybrown.net (personal home page)

Research Theme

Cellular and Molecular Neuroscience

Interests

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.

Inflammatory-activated glia killing co-cultured neurons
Inflammatory-activated glia killing co-cultured neurons
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Research Focus

Keywords

Microglia

Inflammation

Nitric oxide

Phagocytosis

Mitochondria

Clinical conditions

Alzheimer's disease

Cerebrovascular disorders

Dementia

Encephalitis

Meningitis

Parkinson's disease

Stroke

Traumatic brain injury

Equipment

Cell culture

Enzyme assays

Fluorescence microscopy

Immunohistochemistry

Microscopy

Collaborators

No collaborators listed

Associated News Items


Publications

2013

Borutaite V, Toleikis A, Brown GC (2013), “In the eye of the storm: mitochondrial damage during heart and brain ischaemia.” FEBS J 280(20):4999-5014 Details

Emmrich JV, Hornik TC, Neher JJ, Brown GC (2013), “Rotenone induces neuronal death by microglial phagocytosis of neurons.” FEBS J 280(20):5030-8 Details

Fricker M, Vilalta A, Tolkovsky AM, Brown GC (2013), “Caspase inhibitors protect neurons by enabling selective necroptosis of inflamed microglia.” J Biol Chem 288(13):9145-52 Details

Hornik TC, Neniskyte U, Brown GC (2013), “Inflammation induces Multinucleation of Microglia via PKC inhibition of Cytokinesis, generating highly phagocytic Multinucleated Giant Cells.” J Neurochem Details

Neher JJ, Emmrich JV, Fricker M, Mander PK, Théry C, Brown GC (2013), “Phagocytosis executes delayed neuronal death after focal brain ischemia.” Proc Natl Acad Sci U S A 110(43):E4098-107 Details

Neniskyte U, Brown GC (2013), “Analysis of microglial production of reactive oxygen and nitrogen species.” Methods Mol Biol 1041:103-11 Details

Neniskyte U, Brown GC (2013), “Lactadherin/MFG-E8 is essential for microglia-mediated neuronal loss and phagoptosis induced by amyloid β.” J Neurochem 126(3):312-7 Details

2012

Brown GC, Neher JJ (2012), “Eaten alive! Cell death by primary phagocytosis: 'phagoptosis'.” Trends Biochem Sci 37(8):325-32 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

Fricker M, Oliva-Martín MJ, Brown GC (2012), “Primary phagocytosis of viable neurons by microglia activated with LPS or Aβ is dependent on calreticulin/LRP phagocytic signalling.” J Neuroinflammation 9:196 Details

Neher JJ, Neniskyte U, Brown GC (2012), “Primary phagocytosis of neurons by inflamed microglia: potential roles in neurodegeneration.” Front Pharmacol 3:27 Details

2011

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

2010

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

2009

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

2008

Brown GC, Borutaite V (2008), “Regulation of apoptosis by the redox state of cytochrome c.” Biochim Biophys Acta 1777(7-8):877-81 Details

2007

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

Brown GC (2007), “Mechanisms of inflammatory neurodegeneration: iNOS and NADPH oxidase.” Biochem Soc Trans 35(Pt 5):1119-21 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

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

2006

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

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 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

2005

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

2004

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

2003

Brown GC, Bal-Price A (2003), “Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria.” Mol Neurobiol 27(3):325-55 Details

2002

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

2001

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