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Department
  • Biochemistry
  • Research Focus

    Keywords

  • Microglia
  • Neuroinflammation
  • Neurodegeneration
  • Phagocytosis
  • Clinical Conditions

  • Alzheimer's disease
  • Parkinson's disease
  • Equipment & Techniques

  • Cell culture
  • Enzyme assays
  • Fluorescence microscopy
  • Immunohistochemistry
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    Professor Guy Brown

    University Position
    Professor

    Interests

    We 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.

    Microglia in the hippocampus

    Microglia (green) and neuronal cell bodies (red) in the hippocampus of mice exposed to amyloid beta, which greatly increases microglial phagocytosis of neuronal cell bodies (appearing yellow within the microglia).

    Key Publications

    The Endotoxin Hypothesis of Parkinson’s Disease.

    DOI: http://doi.org/10.1002/mds.29432
    Journal: Movement Disorders
    E-pub date: 1 Jul 2023
    Authors: GC Brown, M Camacho, CH Williams-Gray

    Publications

    Cell death by phagocytosis.

    DOI: http://doi.org/10.1038/s41577-023-00921-6
    Journal: Nat Rev Immunol
    E-pub date: 1 Feb 2024
    Authors: GC Brown

    P2Y6 receptor-dependent microglial phagocytosis of synapses during development regulates synapse density and memory.

    DOI: http://doi.org/10.1523/JNEUROSCI.1089-23.2023
    Journal: J Neurosci
    E-pub date: 29 Nov 2023
    Authors: JM Dundee, M Puigdellívol, R Butler, GC Brown

    Syk inhibitors protect against microglia-mediated neuronal loss in culture.

    DOI: http://doi.org/10.3389/fnagi.2023.1120952
    Journal: Front Aging Neurosci
    E-pub date: 1 Aug 2023
    Authors: TJY Birkle, GC Brown

    Extracellular tau stimulates phagocytosis of living neurons by activated microglia via Toll-like 4 receptor-NLRP3 inflammasome-caspase-1 signalling axis.

    DOI: http://doi.org/10.1038/s41598-023-37887-3
    Journal: Sci Rep
    E-pub date: 4 Jul 2023
    Authors: K Pampuscenko, R Morkuniene, L Krasauskas, V Smirnovas, GC Brown, V Borutaite

    Alzheimer’s disease-associated R47H TREM2 increases, but wild-type TREM2 decreases, microglial phagocytosis of synaptosomes and neuronal loss.

    DOI: http://doi.org/10.1002/glia.24318
    Journal: Glia
    E-pub date: 1 Apr 2023
    Authors: AS Popescu, CA Butler, DH Allendorf, TM Piers, A Mallach, J Roewe, P Reinhardt, A Cinti, L Redaelli, C Boudesco, L Pradier, JM Pocock, P Thornton, GC Brown

    P2Y6 receptor-dependent microglial phagocytosis of synapses mediates synaptic and memory loss in aging.

    DOI: http://doi.org/10.1111/acel.13761
    Journal: Aging Cell
    E-pub date: 1 Feb 2023
    Authors: JM Dundee, M Puigdellívol, R Butler, TOJ Cockram, GC Brown

    Microglia states and nomenclature: A field at its crossroads.

    DOI: http://doi.org/10.1016/j.neuron.2022.10.020
    Journal: Neuron
    E-pub date: 2 Nov 2022
    Authors: RC Paolicelli, A Sierra, B Stevens, M-E Tremblay, A Aguzzi, B Ajami, I Amit, E Audinat, I Bechmann, M Bennett, F Bennett, A Bessis, K Biber, S Bilbo, M Blurton-Jones, E Boddeke, D Brites, B Brône, GC Brown, O Butovsky, MJ Carson, B Castellano, M Colonna, SA Cowley, C Cunningham, D Davalos, PL De Jager, B de Strooper, A Denes, BJL Eggen, U Eyo, E Galea, S Garel, F Ginhoux, CK Glass, O Gokce, D Gomez-Nicola, B González, S Gordon, MB Graeber, AD Greenhalgh, P Gressens, M Greter, DH Gutmann, C Haass, MT Heneka, FL Heppner, S Hong, DA Hume, S Jung, H Kettenmann, J Kipnis, R Koyama, G Lemke, M Lynch, A Majewska, M Malcangio, T Malm, R Mancuso, T Masuda, M Matteoli, BW McColl, VE Miron, AV Molofsky, M Monje, E Mracsko, A Nadjar, JJ Neher, U Neniskyte, H Neumann, M Noda, B Peng, F Peri, VH Perry, PG Popovich, C Pridans, J Priller, M Prinz, D Ragozzino, RM Ransohoff, MW Salter, A Schaefer, DP Schafer, M Schwartz, M Simons, CJ Smith, WJ Streit, TL Tay, L-H Tsai, A Verkhratsky, R von Bernhardi, H Wake, V Wittamer, SA Wolf, L-J Wu, T Wyss-Coray

    Brain Cells Release Calreticulin That Attracts and Activates Microglia, and Inhibits Amyloid Beta Aggregation and Neurotoxicity.

    DOI: http://doi.org/10.3389/fimmu.2022.859686
    Journal: Front Immunol
    E-pub date: 1 Aug 2022
    Authors: KM Reid, EJA Kitchener, CA Butler, TOJ Cockram, GC Brown

    Knockout of the P2Y6 Receptor Prevents Peri-Infarct Neuronal Loss after Transient, Focal Ischemia in Mouse Brain.

    DOI: http://doi.org/10.3390/ijms23042304
    Journal: International Journal of Molecular Sciences
    E-pub date: 21 Feb 2022
    Authors: S Milde, GC Brown

    Does Soluble TREM2 Protect Against Alzheimer’s Disease?

    DOI: http://doi.org/10.3389/fnagi.2021.834697
    Journal: Frontiers in Aging Neuroscience
    E-pub date: 28 Jan 2022
    Authors: GC Brown, P St George-Hyslop

    The microglial P2Y6 receptor mediates neuronal loss and memory deficits in neurodegeneration.

    DOI: http://doi.org/10.1016/j.celrep.2021.110148
    Journal: Cell Rep
    E-pub date: 28 Dec 2021
    Authors: M Puigdellívol, S Milde, A Vilalta, TOJ Cockram, DH Allendorf, JY Lee, JM Dundee, K Pampuščenko, V Borutaite, HN Nuthall, JH Brelstaff, MG Spillantini, GC Brown

    Inflammatory neuronal loss in the substantia nigra induced by systemic lipopolysaccharide is prevented by knockout of the P2Y6 receptor in mice.

    DOI: http://doi.org/10.1186/s12974-021-02280-2
    Journal: J Neuroinflammation
    E-pub date: 11 Oct 2021
    Authors: S Milde, FW van Tartwijk, A Vilalta, TC Hornik, JM Dundee, M Puigdellívol, GC Brown

    Microglial phagocytosis of neurons in neurodegeneration, and its regulation.

    DOI: http://doi.org/10.1111/jnc.15327
    Journal: J Neurochem
    E-pub date: 31 Aug 2021
    Authors: CA Butler, AS Popescu, EJA Kitchener, DH Allendorf, M Puigdellívol, GC Brown

    Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer’s R47H mutant increases Aβ aggregation.

    DOI: http://doi.org/10.1016/j.jbc.2021.100631
    Journal: J Biol Chem
    E-pub date: 1 Aug 2021
    Authors: A Vilalta, Y Zhou, J Sevalle, JK Griffin, K Satoh, DH Allendorf, S De, M Puigdellívol, A Bruzas, MA Burguillos, RB Dodd, F Chen, Y Zhang, P Flagmeier, L-M Needham, M Enomoto, S Qamar, J Henderson, J Walter, PE Fraser, D Klenerman, SF Lee, P St George-Hyslop, GC Brown

    The Phagocytic Code Regulating Phagocytosis of Mammalian Cells.

    DOI: http://doi.org/10.3389/fimmu.2021.629979
    Journal: Front Immunol
    E-pub date: 1 Aug 2021
    Authors: TOJ Cockram, JM Dundee, AS Popescu, GC Brown

    Sialylation acts as a checkpoint for innate immune responses in the central nervous system.

    DOI: http://doi.org/10.1002/glia.23945
    Journal: Glia
    E-pub date: 1 Jul 2021
    Authors: C Klaus, H Liao, DH Allendorf, GC Brown, H Neumann

    Lipopolysaccharide activates microglia via neuraminidase 1 desialylation of Toll-like Receptor 4.

    DOI: http://doi.org/10.1111/jnc.15024
    Journal: J Neurochem
    E-pub date: 1 Nov 2020
    Authors: DH Allendorf, EH Franssen, GC Brown

    Extracellular tau induces microglial phagocytosis of living neurons in cell cultures.

    DOI: http://doi.org/10.1111/jnc.14940
    Journal: J Neurochem
    E-pub date: 31 Aug 2020
    Authors: K Pampuscenko, R Morkuniene, T Sneideris, V Smirnovas, R Budvytyte, G Valincius, GC Brown, V Borutaite

    Sialylation and Galectin-3 in Microglia-Mediated Neuroinflammation and Neurodegeneration.

    DOI: http://doi.org/10.3389/fncel.2020.00162
    Journal: Front Cell Neurosci
    E-pub date: 1 Aug 2020
    Authors: M Puigdellívol, DH Allendorf, GC Brown

    TET2 Regulates the Neuroinflammatory Response in Microglia.

    DOI: http://doi.org/10.1016/j.celrep.2019.09.013
    Journal: Cell Rep
    E-pub date: 15 Oct 2019
    Authors: A Carrillo-Jimenez, Ö Deniz, MV Niklison-Chirou, R Ruiz, K Bezerra-Salomão, V Stratoulias, R Amouroux, PK Yip, A Vilalta, M Cheray, AM Scott-Egerton, E Rivas, K Tayara, I García-Domínguez, J Garcia-Revilla, JC Fernandez-Martin, AM Espinosa-Oliva, X Shen, P St George-Hyslop, GC Brown, P Hajkova, B Joseph, JL Venero, MR Branco, MA Burguillos

    The endotoxin hypothesis of neurodegeneration.

    DOI: http://doi.org/10.1186/s12974-019-1564-7
    Journal: J Neuroinflammation
    E-pub date: 13 Sep 2019
    Authors: GC Brown

    Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease.

    DOI: http://doi.org/10.1007/s00401-019-02013-z
    Journal: Acta Neuropathol
    E-pub date: 31 Aug 2019
    Authors: A Boza-Serrano, R Ruiz, R Sanchez-Varo, J García-Revilla, Y Yang, I Jimenez-Ferrer, A Paulus, M Wennström, A Vilalta, D Allendorf, JC Davila, J Stegmayr, S Jiménez, MA Roca-Ceballos, V Navarro-Garrido, M Swanberg, CL Hsieh, LM Real, E Englund, S Linse, H Leffler, UJ Nilsson, GC Brown, A Gutierrez, J Vitorica, JL Venero, T Deierborg

    Calreticulin and Galectin-3 Opsonise Bacteria for Phagocytosis by Microglia.

    DOI: http://doi.org/10.3389/fimmu.2019.02647
    Journal: Front Immunol
    E-pub date: 1 Aug 2019
    Authors: TOJ Cockram, M Puigdellívol, GC Brown

    TET2 regulates the neuroinflammatory response in microglia

    DOI: http://doi.org/10.1101/592055
    Journal:
    E-pub date: 1 Aug 2019
    Authors: A Carrillo-Jimenez, Ö Deniz, MV Niklison-Chirou, R Ruiz, K Bezerra-Salomão, V Stratoulias, R Amouroux, PK Yip, A Vilalta, M Cheray, AM Scott-Egerton, E Rivas, K Tayara, I García-Domínguez, J Garcia-Revilla, JC Fernandez-Martin, AM Espinosa-Oliva, X Shen, P StGeorge-Hyslop, GC Brown, P Hajkova, B Joseph, J Venero, MR Branco, MA Burguillos

    How the brain eats itself

    DOI: http://doi.org/10.1042/bio04101032
    Journal: Biochemist
    E-pub date: 1 Jan 2019
    Authors: D Allendorf, A Popescu, GC Brown

    Effective Knockdown of Gene Expression in Primary Microglia With siRNA and Magnetic Nanoparticles Without Cell Death or Inflammation.

    DOI: http://doi.org/10.3389/fncel.2018.00313
    Journal: Front Cell Neurosci
    E-pub date: 1 Aug 2018
    Authors: A Carrillo-Jimenez, M Puigdellívol, A Vilalta, JL Venero, GC Brown, P StGeorge-Hyslop, MA Burguillos

    Galectin-3, A Novel Endogenous Trem2 Ligand, Regulates Inflammatory Response and Aβ Fibrilation in Alzheimer’s Disease

    DOI: http://doi.org/10.1101/477927
    Journal:
    E-pub date: 1 Aug 2018
    Authors: A Boza-Serrano, R Ruiz, R Sanchez-Varo, Y Yang, J García-Revilla, I Jimenez-Ferrer, A Paulus, M Wennström, A Vilalta, D Allendorf, JC Davila, C Dunning, J Stegmayr, S Jiménez, MA Roca-Ceballos, V Navarro-Garrido, M Swanberg, C Hsieh, L Miguel-Real, E Englund, S Linse, H Leffler, U Nilsson, A Gutierrez, G Brown, J Vitorica, JL Venero, T Deierborg, The Netherland Brain

    Neuronal Cell Death.

    DOI: http://doi.org/10.1152/physrev.00011.2017
    Journal: Physiol Rev
    E-pub date: 1 Apr 2018
    Authors: M Fricker, AM Tolkovsky, V Borutaite, M Coleman, GC Brown

    Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin-3, and Mer Tyrosine Kinase.

    DOI: http://doi.org/10.4049/jimmunol.1502532
    Journal: J Immunol
    E-pub date: 15 Jun 2017
    Authors: K Nomura, A Vilalta, DH Allendorf, TC Hornik, GC Brown

    Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration.

    DOI: http://doi.org/10.1038/srep41689
    Journal: Sci Rep
    E-pub date: 27 Jan 2017
    Authors: PK Yip, A Carrillo-Jimenez, P King, A Vilalta, K Nomura, CC Chau, AMS Egerton, Z-H Liu, AJ Shetty, JL Tremoleda, M Davies, T Deierborg, JV Priestley, GC Brown, AT Michael-Titus, JL Venero, MA Burguillos

    Amyloid β induces microglia to phagocytose neurons via activation of protein kinase Cs and NADPH oxidase.

    DOI: http://doi.org/10.1016/j.biocel.2016.06.005
    Journal: Int J Biochem Cell Biol
    E-pub date: 1 Dec 2016
    Authors: U Neniskyte, M Fricker, GC Brown

    How microglia kill neurons.

    DOI: http://doi.org/10.1016/j.brainres.2015.08.031
    Journal: Brain Res
    E-pub date: 2 Dec 2015
    Authors: GC Brown, A Vilalta

    Neuroinflammation in Alzheimer’s disease.

    DOI: http://doi.org/10.1016/S1474-4422(15)70016-5
    Journal: Lancet Neurol
    E-pub date: 1 Apr 2015
    Authors: MT Heneka, MJ Carson, J El Khoury, GE Landreth, F Brosseron, DL Feinstein, AH Jacobs, T Wyss-Coray, J Vitorica, RM Ransohoff, K Herrup, SA Frautschy, B Finsen, GC Brown, A Verkhratsky, K Yamanaka, J Koistinaho, E Latz, A Halle, GC Petzold, T Town, D Morgan, ML Shinohara, VH Perry, C Holmes, NG Bazan, DJ Brooks, S Hunot, B Joseph, N Deigendesch, O Garaschuk, E Boddeke, CA Dinarello, JC Breitner, GM Cole, DT Golenbock, MP Kummer

    Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis.

    DOI: http://doi.org/10.1016/j.febslet.2014.05.046
    Journal: FEBS Lett
    E-pub date: 25 Aug 2014
    Authors: U Neniskyte, A Vilalta, GC Brown

    Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis

    DOI: http://doi.org/10.1016/j.febslet.2014.05.04
    Journal: FEBS Letters
    E-pub date: 6 Jun 2014
    Authors: U Neniskyte, A Vilalta, GC Brown

    Microglial phagocytosis of live neurons.

    DOI: http://doi.org/10.1038/nrn3710
    Journal: Nat Rev Neurosci
    E-pub date: 1 Apr 2014
    Authors: GC Brown, JJ Neher