EMAIL gcb3@cam.ac.uk

Department

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Research Theme Beyond the Neuron Lifelong Brain Development and Brain Ageing Neurons, Circuits and Networks

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 Alzheimer’s disease

DOI: http://doi.org/10.1186/s13024-024-00722-y
Journal: Molecular Neurodegeneration
E-pub date: 1 Apr 2024
Authors: GC Brown, MT Heneka

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

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

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

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

Publications

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: 26 Jul 2024
Authors: S Milde, GC Brown

Disease phenotypic screening in neuron-glia cocultures identifies blockers of inflammatory neurodegeneration.

DOI: http://doi.org/10.1016/j.isci.2024.109454
Journal: iScience
E-pub date: 19 Apr 2024
Authors: TJY Birkle, HMG Willems, J Skidmore, 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

Activated microglia release β-galactosidase that promotes inflammatory neurodegeneration.

DOI: http://doi.org/10.3389/fnagi.2023.1327756
Journal: Front Aging Neurosci
E-pub date: 1 Aug 2023
Authors: EJA Kitchener, JM Dundee, 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

Neu1 Is Released From Activated Microglia, Stimulating Microglial Phagocytosis and Sensitizing Neurons to Glutamate.

DOI: http://doi.org/10.3389/fncel.2022.917884
Journal: Front Cell Neurosci
E-pub date: 1 Aug 2022
Authors: DH Allendorf, 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

Neuronal Loss after Stroke Due to Microglial Phagocytosis of Stressed Neurons.

DOI: http://doi.org/10.3390/ijms222413442
Journal: Int J Mol Sci
E-pub date: 14 Dec 2021
Authors: 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

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

CD33M inhibits microglial phagocytosis, migration and proliferation, but the Alzheimer’s disease-protective variant CD33m stimulates phagocytosis and proliferation, and inhibits adhesion.

DOI: http://doi.org/10.1111/jnc.15349
Journal: J Neurochem
E-pub date: 1 Jul 2021
Authors: CA Butler, P Thornton, GC Brown

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

Activated microglia desialylate their surface, stimulating complement receptor 3-mediated phagocytosis of neurons.

DOI: http://doi.org/10.1002/glia.23757
Journal: Glia
E-pub date: 1 May 2020
Authors: DH Allendorf, M Puigdellívol, 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

Neurophagy, the phagocytosis of live neurons and synapses by glia, contributes to brain development and disease.

DOI: http://doi.org/10.1111/febs.14323
Journal: FEBS J
E-pub date: 1 Oct 2018
Authors: A Vilalta, 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

Anti-CD47 antibodies induce phagocytosis of live, malignant B cells by macrophages via the Fc domain, resulting in cell death by phagoptosis.

DOI: http://doi.org/10.18632/oncotarget.18492
Journal: Oncotarget
E-pub date: 22 Sep 2017
Authors: LE Métayer, A Vilalta, GAA Burke, 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

Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis.

DOI: http://doi.org/10.1242/jcs.174631
Journal: J Cell Sci
E-pub date: 1 Jan 2016
Authors: TC Hornik, A Vilalta, 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

Phagoptosis – Cell Death By Phagocytosis – Plays Central Roles in Physiology, Host Defense and Pathology.

DOI: http://doi.org/10.2174/156652401509151105130628
Journal: Curr Mol Med
E-pub date: 1 Aug 2015
Authors: GC Brown, A Vilalta, M Fricker

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

Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo.

DOI: http://doi.org/10.1002/glia.22693
Journal: GLIA
E-pub date: 1 Jan 2014
Authors: JJ Neher, U Neniskyte, T Hornik, GC Brown

Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation.

DOI: http://doi.org/10.1111/j.1471-4159.2005.03422.x
Journal: J Neurochem
E-pub date: 1 Nov 2005
Authors: A Kinsner, V Pilotto, S Deininger, GC Brown, S Coecke, T Hartung, A Bal-Price

Different pathways for iNOS-mediated toxicity in vitro dependent on neuronal maturation and NMDA receptor expression.

DOI: http://doi.org/10.1046/j.1471-4159.2002.00973.x
Journal: J Neurochem
E-pub date: 1 Jul 2002
Authors: S Golde, S Chandran, GC Brown, A Compston