An engineered fusion protein exploits the efferocytosis pathway to clear amyloid-β (Aβ) from the brain without eliciting the severe inflammatory adverse effects associated with Aβ-targeting antibody-based immunotherapies. In mouse models of Alzheimer’s disease, this approach induced robust clearance of Aβ without inflammation, improved synapse protection, and decreased brain microhemorrhage, which result in superior behavioral recovery.
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References
Busche, M. A. & Hyman, B. T. Synergy between amyloid-beta and tau in Alzheimer’s disease. Nat. Neurosci. 23, 1183–1193 (2020). A review article that presents the complex interaction between Aβ and tau in AD pathogenesis.
Sevigny, J. et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature 537, 50–56 (2016). A paper that reports the efficacy and safety data from a phase 1b randomized trial of aducanumab.
Fuller, J. P., Stavenhagen, J. B. & Teeling, J. L. New roles for Fc receptors in neurodegeneration—the impact on immunotherapy for Alzheimer’s disease. Front. Neurosci. 8, 235 (2014). A review article that suggests that activation of inflammatory FcRs in the central nervous system may have harmful consequences.
Doran, A. C., Yurdagul, A. Jr. & Tabas, I. Efferocytosis in health and disease. Nat. Rev. Immunol. 20, 254–267 (2020). A review article that presents how phagocytes take up and process apoptotic cells.
Lemke, G. Biology of the TAM receptors. Cold Spring Harb. Perspect. Biol. 5, a009076 (2013). A review article that presents how TAM receptor–ligand signaling controls the innate immune response.
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This is a summary of: Jung, H. et al. Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nat. Med. https://doi.org/10.1038/s41591-022-01926-9 (2022).
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Toward inflammation-free therapeutics in Alzheimer’s disease. Nat Med 28, 1765–1766 (2022). https://doi.org/10.1038/s41591-022-01972-3
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DOI: https://doi.org/10.1038/s41591-022-01972-3
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