We show that genetic disruption of TFEB- and vacuolar ATPase-mediated lysosomal signaling leads to increased tau pathology and defective microglia activation. Our findings demonstrate an essential role of the lysosome in regulating microglia activity in tauopathy and Alzheimer’s disease.
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References
Colacurcio, D. J. & Nixon, R. A. Disorders of lysosomal acidification–the emerging role of v-ATPase in aging and neurodegenerative disease. Ageing Res. Rev. 32, 75–88 (2016). This article summarizes evidence that links dysfunction of the v-ATPase complex to neurodegenerative diseases.
Martini-Stoica, H. et al. The autophagy-lysosomal pathway in neurodegeneration: a TFEB perspective. Trends Neurosci. 39, 221–234 (2016). This review discusses the regulation of TFEB in the autophagy–lysosomal pathway and its function in neurodegenerative diseases.
Leng, F. & Edison, P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat. Rev. Neurol. 17, 157–172 (2021). This review discusses the effect of neuroinflammation in the disease trajectory in Alzheimer’s disease, with a focus on microglia.
Ballabio, A. & Bonifacino, J. S. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat. Rev. Mol. Cell Biol. 21, 101–118 (2020). This article reviews recent discoveries that highlight the lysosome as a regulatory hub for cellular and organismal homeostasis.
Ulland, T. K. et al. TREM2 maintains microglial metabolic fitness in Alzheimer’s disease. Cell 170, 649–663.e613 (2017). This paper shows that TREM2 regulates microglial metabolism and bioenergics via mTOR signaling and that TREM2 loss-of-function-induced metabolic defects can be rescued by boosting ATP levels.
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This is a summary of: Wang, B. et al. TFEB–vacuolar ATPase signaling regulates lysosomal function and microglial activation in tauopathy. Nat. Neurosci. https://doi.org/10.1038/s41593-023-01494-2 (2023).
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Lysosome regulation of microglia in Alzheimer’s disease via TFEB–vacuolar ATPase. Nat Neurosci 27, 13–14 (2024). https://doi.org/10.1038/s41593-023-01495-1
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DOI: https://doi.org/10.1038/s41593-023-01495-1
