Phenotyping and genetic interrogation of microglia in Alzheimer's disease models
Dr. Ikezu has made significant contributions to the classification of the activation phenotype of microglia. These studies identified miR-155, APOE and TREM2 as key molecules for shaping neurodegenerative microglia, which also are genetically associated with Alzheimer's disease. This work is reframing the biology of microglia and its disease implications.
References
- Yin Z, Herron S, Silveira S, Kleemann K, Gauthier C, Mallah D, Cheng Y, Margeta MA, Pitts KM, Barry JL, Subramanian A, Shorey H, Brandao W, Durao A, Delpech JC, Madore C, Jedrychowski M, Ajay AK, Murugaiyan G, Hersh SW, Ikezu S, Ikezu T, Butovsky O. Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease. Nature Neuroscience. 2023; doi:10.1038/s41593-023-01355-y.
- Yin Z, Rosenzweig N, Kleemann KL, Zhang X, Brandão W, Margeta MA, Schroeder C, Sivanathan KN, Silveira S, Gauthier C, Mallah D, Pitts KM, Durao A, Herron S, Shorey H, Cheng Y, Barry JL, Krishnan RK, Wakelin S, Rhee J, Yung A, Aronchik M, Wang C, Jain N, Bao X, Gerrits E, Brouwer N, Deik A, Tenen DG, Ikezu T, Santander NG, McKinsey GL, Baufeld C, Sheppard D, Krasemann S, Nowarski R, Eggen BJL, Clish C, Tanzi RE, Madore C, Arnold TD, Holtzman DM, Butovsky O. APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFβ-mediated checkpoints. Nature Immunology. 2023; doi:10.1038/s41590-023-01627-6.
- Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, Beckers L, O'Loughlin E, Xu Y, Fanek Z, Greco DJ, Smith ST, Tweet G, Humulock Z, Zrzavy T, Conde-Sanroman P, Gacias M, Weng Z, Chen H, Tjon E, Mazaheri F, Hartmann K, Madi A, Ulrich JD, Glatzel M, Worthmann A, Heeren J, Budnik B, Lemere C, Ikezu T, Heppner FL, Litvak V, Holtzman DM, Lassmann H, Weiner HL, Ochando J, Haass C, Butovsky O. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 2017; doi:10.1016/j.immuni.2017.08.008.
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