Professor Guy Brown University positionProfessor Professor Guy Brown is pleased to consider applications from prospective PhD students. DepartmentsHome pagehttp://www.guybrown.net (personal home page) Research ThemeInterestsWe are interested in the mechanisms of neuroinflammation and neurodegeneration in the brain. We use mouse models of disease and cultured brain cells to investigate how microglia become activated by inflammatory stimuli and how such microglia damage or protect neurons. We are particularly interested in the roles of microglial phagocytosis in neurodegeneration, as we have found that inflamed microglial can phagocytose (i.e. eat) live neurons and neuronal parts such as synapses. And so we are trying to find ways to prevent this.  Inflammatory-activated glia killing co-cultured neurons Click image to view full-size Research Focus
EquipmentCell culture Enzyme assays Fluorescence microscopy Immunohistochemistry Microscopy CollaboratorsNo collaborators listed Associated News Items
Publications2021Birkle T, Brown GC. (2021), “I'm Infected, Eat Me! Innate Immunity Mediated by Live, Infected Cells Signaling To Be Phagocytosed” Infect Immun 89(5):e00476-20 Brown G.C. (2021), “Neuronal Loss after Stroke Due to Microglial Phagocytosis of Stressed Neurons” Int J Mol Sci . 22(24):13442 Butler CA, Popescu AS, Kitchener EJA, Allendorf DH, Puigdellívol M, Brown GC. (2021), “Microglial phagocytosis of neurons in neurodegeneration, and its regulation” J Neurochem 158(3):621-639 Butler CA, Thornton P, Brown GC. (2021), “CD33M inhibits microglial phagocytosis, migration and proliferation, but the Alzheimer's disease-protective variant CD33m stimulates phagocytosis and proliferation, and inhibits adhesion” J Neurochem. 158(2):297-310 Cockram TOJ, Dundee JM, Popescu AS, Brown GC. (2021), “The Phagocytic Code Regulating Phagocytosis of Mammalian Cells” Front Immunol. 12:629979. Klaus C, Liao H, Allendorf DH, Brown GC, Neumann H. (2021), “Sialylation acts as a checkpoint for innate immune responses in the central nervous system.” Glia 69(7):1619-1636 Milde S, van Tartwijk FW, Vilalta A, Hornik TC, Dundee JM, Puigdellívol M, Brown GC. (2021), “Inflammatory neuronal loss in the substantia nigra induced by systemic lipopolysaccharide is prevented by knockout of the P2Y 6 receptor in mice” J Neuroinflammation 18(1):225 Puigdellívol M, Milde S, Vilalta A, Cockram TOJ, Allendorf DH, Lee JY, Dundee JM, Pampuš?enko K, Borutaite V, Nuthall HN, Brelstaff JH, Spillantini MG, Brown GC. (2021), “The microglial P2Y 6 receptor mediates neuronal loss and memory deficits in neurodegeneration” Cell Rep. 37(13):110148 Vilalta A, Zhou Y, Sevalle J, Griffin JK, Satoh K, Allendorf DH, De S, Puigdellívol M, Bruzas A, Burguillos MA, Dodd RB, Chen F, Zhang Y, Flagmeier P, Needham LM, Enomoto M, Qamar S, Henderson J, Walter J, Fraser PE, Klenerman D, Lee SF, St George-Hyslop P, Brown GC. (2021), “Wild-type sTREM2 blocks A? aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases A? aggregation” J Biol Chem 2020Allendorf DH, Franssen EH, Brown GC. (2020), “Lipopolysaccharide activates microglia via neuraminidase 1 desialylation of Toll-like Receptor 4” J Neurochem. 155(4):403-416. Pampuscenko K, Morkuniene R, Sneideris T, Smirnovas V, Budvytyte R, Valincius G, Brown GC, Borutaite V. (2020), “Extracellular tau induces microglial phagocytosis of living neurons in cell cultures” J Neurochem. 154(3):316-329 Puigdellívol M, Allendorf DH, Brown GC. (2020), “Sialylation and Galectin-3 in Microglia-Mediated Neuroinflammation and Neurodegeneration.” Front Cell Neurosci. 14:162 2019Boza-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. 2018Carrillo-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 2017Brown 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. 2016Hornik 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 ? induces microglia to phagocytose neurons via activation of protein kinase Cs and NADPH oxidase.” Int J Biochem Cell Biol. 81(Pt B):346-355 2015Heneka 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 2014Brown 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 2013Borutaite 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 ?.” J Neurochem 126(3):312-7 Details 2012Brown 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 A? 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 2011Brown 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 ? is mediated by primary phagocytosis of neurons by microglia.” J Biol Chem 286(46):39904-13 Details 2010Brown 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 2009Brown 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 2008Brown GC, Borutaite V (2008), “Regulation of apoptosis by the redox state of cytochrome c.” Biochim Biophys Acta 1777(7-8):877-81 Details 2007Borutaite 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 2006Bal-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 2005Mander 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 2004Brown 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 2003Brown GC, Bal-Price A (2003), “Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria.” Mol Neurobiol 27(3):325-55 Details 2002Bal-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 2001Bal-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 |