Microglia in neuroinflammation and neurodegeneration.
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 can damage or protect neurons. We are particularly interested in the roles of microglial phagocytosis in neurodegeneration, as we have found that inflamed microglia can phagocytose (i.e. eat) live neurons and neuronal parts such as synapses. And so we are trying to find ways to prevent this.
Research objectives
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Understand the roles of microglia in neuroinflammation and neurodegeneration.
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Determine how to prevent excessive microglial phagocytosis of neurons and synapses in neurodegenerative diseases.
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Understand the roles of cell death by phagocytosis in the body and in the brain.
Key publications
Brown GC (2019). The endotoxin hypothesis of neurodegeneration. J. Neuroinflammation, 16(1):180. doi: 10.1186/s12974-019-1564-7
Allendorf DH, Puigdellívol M, Brown GC (2019). Activated microglia desialylate their surface, stimulating complement receptor 3-mediated phagocytosis of neurons. Glia, 10:2647. doi: 10.1002/glia.23757
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. doi: 10.1007/s00401-019-02013-z
Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC (2018). Neuronal Cell Death. Physiol. Rev., 98(2):813-880. doi: 10.1152/physrev.00011.2017
Vilalta A, Brown GC (2018). Neurophagy, the phagocytosis of live neurons and synapses by glia, contributes to brain development and disease. FEBS J., 285(19):3566-3570. doi: 10.1111/febs.14323