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Loss of C9orf72 in Microglia Drives Neuronal Injury by Enhancing Synaptic Pruning in Aged and Alzheimer’s Disease Mice

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References

  1. Goodman LD, Bonini NM. New roles for canonical transcription factors in repeat expansion diseases. Trends Genet 2020, 36: 81–92.

  2. Hao ZB, Wang R, Ren HG, Wang GH. Role of the C9ORF72 gene in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Neurosci Bull 2020, 36: 1057–1070.

  3. Harms M, Benitez BA, Cairns N, Cooper B, Cooper P, Mayo K, et al. C9orf72 hexanucleotide repeat expansions in clinical Alzheimer disease. JAMA Neurol 2013, 70: 736–741.

  4. Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer's disease. Nat Rev Dis Primers 2015, 1: 15056.

  5. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med 2016, 8: 595–608.

  6. Hansen DV, Hanson JE, Sheng M. Microglia in Alzheimer's disease. J Cell Biol 2018, 217: 459–472.

  7. Stephan AH, Barres BA, Stevens B. The complement system: An unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci 2012, 35: 369–389.

  8. McCauley ME, O'Rourke JG, Yáñez A, Markman JL, Ho R, Wang XC, et al. C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature 2020, 585: 96–101.

  9. Lall D, Lorenzini I, Mota TA, Bell S, Mahan TE, Ulrich JD, et al. C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation. Neuron 2021, 109: 2275–2291.e8.

  10. Burk K, Pasterkamp RJ. Disrupted neuronal trafficking in amyotrophic lateral sclerosis. Acta Neuropathol 2019, 137: 859–877.

  11. Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li SM, Ramakrishnan S, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 2016, 352: 712–716.

  12. Ayton S, Bush AI. β-amyloid: The known unknowns. Ageing Res Rev 2021, 65: 101212.

  13. Aw E, Zhang YY, Carroll M. Microglial responses to peripheral type 1 interferon. J Neuroinflammation 2020, 17: 340.

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Acknowledgements

This Research Highlight was supported by the National Natural Science Foundation of China (92049104 and 82103210) and the Research Start-up Project by Hangzhou Normal University (4125C5021920453 and 4125C50220204106).

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Correspondence to Zhihui Huang.

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Wang, M., Jiang, Y. & Huang, Z. Loss of C9orf72 in Microglia Drives Neuronal Injury by Enhancing Synaptic Pruning in Aged and Alzheimer’s Disease Mice. Neurosci. Bull. 38, 327–330 (2022). https://doi.org/10.1007/s12264-021-00796-4

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