Professor Guy Brown
Professor 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.
No collaborators listed
Associated News Items
Boza-Serrano A, Ruiz R, Sanchez-Varo R, García-Revilla J, Yang Y, Jimenez-Ferrer I, Paulus A, Wennström M, Vilalta A, Allendorf D, Davila JC, Stegmayr J, Jiménez S, Roca-Ceballos MA, Navarro-Garrido V, Swanberg M, Hsieh CL, Real LM, Englund E, Linse S, Leffler H, Nilsson UJ, Brown GC, Gutierrez A, Vitorica J, Venero JL, Deierborg T. (2019), “Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer's disease.” Acta Neuropathol. 138(2):251-273.
Brown GC (2019), “The endotoxin hypothesis of neurodegeneration” J Neuroinflammation. 16(1):180
Métayer LE, Brown RD, Carlebur S, Burke GAA, Brown GC. (2019), “Mechanisms of cell death induced by arginase and asparaginase in precursor B-cell lymphoblasts.” Apoptosis. 24(1-2):145-156.
Carrillo-Jimenez A, Puigdellívol M, Vilalta A, Venero JL, Brown GC, StGeorge-Hyslop P, Burguillos MA. (2018), “Effective Knockdown of Gene Expression in Primary Microglia With siRNA and Magnetic Nanoparticles Without Cell Death or Inflammation.” Front Cell Neurosci. 12:313.
Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC (2018), “Neuronal Cell Death” Physiol Rev. 285(19):3566-3575
Brown GC, St George-Hyslop PH (2017), “Deciphering microglial diversity in Alzheimer's disease” Science 356(6343):1123-1124
Métayer LE, Vilalta A, Burke GAA, Brown GC. (2017), “Anti-CD47 antibodies induce phagocytosis of live, malignant B cells by macrophages via the Fc domain, resulting in cell death by phagoptosis.” Oncotarget. 8(37):60892-60903.
Nomura K, Vilalta A, Allendorf DH, Hornik TC, Brown GC. (2017), “Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin-3, and Mer Tyrosine Kinase” J Immunol. 198(12):4792-4801.
Yip PK, Carrillo-Jimenez A, King P, Vilalta A, Nomura K, Chau CC, Egerton AM, Liu ZH, Shetty AJ, Tremoleda JL, Davies M, Deierborg T, Priestley JV, Brown GC, Michael-Titus AT, Venero JL, Burguillos MA. (2017), “Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration.” Sci Rep. 27;7:41689.
Hornik TC, Vilalta A, Brown GC. (2016), “Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis.” J Cell Sci. 129(1):65-79.
Neniskyte U, Fricker M, Brown GC. (2016), “Amyloid β induces microglia to phagocytose neurons via activation of protein kinase Cs and NADPH oxidase.” Int J Biochem Cell Biol. 81(Pt B):346-355
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MP. (2015), “Neuroinflammation in Alzheimer's disease.” Lancet Neurol. 588(17):2952-6
Brown GC, Neher JJ. (2014), “Microglial phagocytosis of live neurons.” Nat Rev Neurosci. 15(4):209-16.
Neher JJ, Neniskyte U, Hornik T, Brown GC. (2014), “Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo.” Glia 62(9):1463-75
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
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
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
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
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
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