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NEUROIMMUNOLOGY IN 2018

Microglia take centre stage in neurodegenerative disease

After many years of being largely neglected in neurodegenerative disease, the past few years have seen a turning point in the field’s view on the impact of microglia in neurological disorders. 2018 has been another exciting year with a number of great contributions in this area.

Key advances

  • LRRC33 regulates the local activation and release of TGFβ1 in the CNS.

  • Senescent microglia and astroglia drive tau phosphorylation and neurofibrillary tangle formation in a non-cell autonomous manner.

  • Mononuclear phagocytes dynamically adapt their phenotype based on astroglial signals.

  • Microglial cell renewal following CSF1R1 inhibition depends on proliferation of surviving CNS-resident microglia.

  • Microglia are involved in TDP43 clearance from neurons and promote recovery from motor symptoms in a mouse model of ALS.

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References

  1. Qin, Y. et al. A milieu molecule for TGFβ required for microglia function in the nervous system. Cell 174, 156–171 (2018).

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  2. Bussian, T. J. et al. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 562, 578–582 (2018).

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  3. Brelstaff, J. et al. Living neurons with tau filaments aberrantly expose phosphatidylserine and are phagocytosed by microglia. Cell Rep. 24, 1939–1948 (2018).

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  4. Locatelli, G. et al. Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model. Nat. Neurosci. 21, 1196–1208 (2018).

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  5. Huang, Y. et al. Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Nat. Neurosci. 21, 530–540 (2018).

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  6. Spiller, K. J. et al. Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy. Nat. Neurosci. 21, 329–340 (2018).

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Acknowledgements

M.T.H. is supported by grants from the Deutsche Forschungsgesellschaft (SFB 1089, excellence cluster ImmunoSensation) and by the European Union Joint Programme–Neurodegenerative Disease (JPND) consortium InCure (funding code 01ED1505A).

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Correspondence to Michael T. Heneka.

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The author declares no competing interests.

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Heneka, M.T. Microglia take centre stage in neurodegenerative disease. Nat Rev Immunol 19, 79–80 (2019). https://doi.org/10.1038/s41577-018-0112-5

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  • DOI: https://doi.org/10.1038/s41577-018-0112-5

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