Microglia require a large amount of energy to clear plaques in the brains of people with Alzheimer’s disease. Leng et al. found that increased activity of the glycolytic enzyme hexokinase 2 (HK2) blocks microglial phagocytosis in Alzheimer’s disease. Inhibition of HK2 results in increased microglial energy production by a compensatory lipid metabolism response, restores phagocytosis and improves cognitive function.
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References
Cummings, J. et al. Alzheimers Dement. (NY) 8, e12295 (2022).
Hansen, D. V., Hanson, J. E. & Sheng, M. J. Cell Biol. 217, 459–472 (2018).
Leng, F. & Edison, P. Nat. Rev. Neurol. 17, 157–172 (2021).
Leng, L. Nat. Metab. https://doi.org/10.1038/s42255-022-00643-4 (2022).
Roberts, D. J. & Miyamoto, S. Cell Death Differ. 22, 248–257 (2015).
Kalsbeek, M. J. T., Mulder, L. & Yi, C.-X. Mol. Cell. Endocrinol. 438, 27–35 (2016).
Baik, S. H. et al. Cell Metab. 30, 493–507.e6 (2019).
O’Neill, L. A. J., Kishton, R. J. & Rathmell, J. Nat. Rev. Immunol. 16, 553–565 (2016).
Pan, R.-Y. et al. Cell Metab. 34, 634–648.e6 (2022).
Camandola, S. & Mattson, M. P. EMBO J. 36, 1474–1492 (2017).
Alhayaza, R., Haque, E., Karbasiafshar, C., Sellke, F. W. & Abid, M. R. Front Chem. 8, 592688 (2020).
Wang, Y., Mohsen, A. W., Mihalik, S. J., Goetzman, E. S. & Vockley, J. J. Biol. Chem. 285, 29834–29841 (2010).
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Choi, H., Mook-Jung, I. Lipid fuel for hungry-angry microglia. Nat Metab 4, 1223–1224 (2022). https://doi.org/10.1038/s42255-022-00647-0
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DOI: https://doi.org/10.1038/s42255-022-00647-0
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