Lee, E. B., Lee, V. M. & Trojanowski, J. Q. Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat. Rev. Neurosci. 13, 38–50 (2011).
Article PubMed PubMed Central Google Scholar
Neumann, M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130–133 (2006).
Article CAS PubMed Google Scholar
McGurk, L. et al. Poly(ADP-ribose) prevents pathological phase separation of TDP-43 by promoting liquid demixing and stress granule localization. Mol. Cell 71, 703–717 (2018).
Article CAS PubMed PubMed Central Google Scholar
Gasset-Rosa, F. et al. Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death. Neuron 102, 339–357 (2019).
Article CAS PubMed PubMed Central Google Scholar
Gu, J. et al. Hsp70 chaperones TDP-43 in dynamic, liquid-like phase and prevents it from amyloid aggregation. Cell Res. 31, 1024–1027 (2021).
Article CAS PubMed PubMed Central Google Scholar
Wang, C. et al. Stress induces dynamic, cytotoxicity-antagonizing TDP-43 nuclear bodies via paraspeckle LncRNA NEAT1-mediated liquid–liquid phase separation. Mol. Cell 79, 443–458 (2020).
Article CAS PubMed Google Scholar
Yu, H. et al. HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science 371, eabb4309 (2021).
Article CAS PubMed Google Scholar
Grese, Z. R. et al. Specific RNA interactions promote TDP-43 multivalent phase separation and maintain liquid properties. EMBO Rep. 22, e53632 (2021).
Article CAS PubMed PubMed Central Google Scholar
Perez-Berlanga, M. et al. Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns. EMBO J. 42, e111719 (2023).
Article CAS PubMed PubMed Central Google Scholar
Taylor, J. P., Brown, R. H. Jr & Cleveland, D. W. Decoding ALS: from genes to mechanism. Nature 539, 197–206 (2016).
Article PubMed PubMed Central Google Scholar
Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).
Article CAS PubMed PubMed Central Google Scholar
Wolozin, B. & Ivanov, P. Stress granules and neurodegeneration. Nat. Rev. Neurosci. 20, 649–666 (2019).
Article CAS PubMed PubMed Central Google Scholar
Mitrea, D. M., Mittasch, M., Gomes, B. F., Klein, I. A. & Murcko, M. A. Modulating biomolecular condensates: a novel approach to drug discovery. Nat. Rev. Drug Discov. 21, 841–862 (2022).
Article CAS PubMed PubMed Central Google Scholar
Vendruscolo, M. & Fuxreiter, M. Protein condensation diseases: therapeutic opportunities. Nat. Commun. 13, 5550 (2022).
Article CAS PubMed PubMed Central Google Scholar
Apicco, D. J. et al. Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo. Nat. Neurosci. 21, 72–80 (2018).
Article CAS PubMed Google Scholar
Becker, L. A. et al. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature 544, 367–371 (2017).
Article CAS PubMed PubMed Central Google Scholar
Hurtle, B. T., Xie, L. & Donnelly, C. J. Disrupting pathologic phase transitions in neurodegeneration. J. Clin. Invest. 133, e168549 (2023).
Article PubMed PubMed Central Google Scholar
Ma, S., Meng, Z., Chen, R. & Guan, K. L. The Hippo Pathway: biology and pathophysiology. Annu. Rev. Biochem. 88, 577–604 (2019).
Article CAS PubMed Google Scholar
Cai, D. et al. Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression. Nat. Cell Biol. 21, 1578–1589 (2019).
Article CAS PubMed PubMed Central Google Scholar
Lu, Y. et al. Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression. Nat. Cell Biol. 22, 453–464 (2020).
Article CAS PubMed PubMed Central Google Scholar
Shao, Y. et al. A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation. Nat. Cell Biol. 26, 86–99 (2024).
Article CAS PubMed Google Scholar
Harvey, K. F., Zhang, X. & Thomas, D. M. The Hippo pathway and human cancer. Nat. Rev. Cancer 13, 246–257 (2013).
Article CAS PubMed Google Scholar
Irwin, M. et al. A positive feedback loop of Hippo- and c-Jun-amino-terminal kinase signaling pathways regulates amyloid-beta-mediated neurodegeneration. Front. Cell Dev. Biol. 8, 117 (2020).
Article PubMed PubMed Central Google Scholar
Lee, J. K. et al. MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS. Proc. Natl Acad. Sci. USA 110, 12066–12071 (2013).
Article CAS PubMed PubMed Central Google Scholar
Wang, W. et al. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nat. Cell Biol. 17, 490–499 (2015).
Article CAS PubMed PubMed Central Google Scholar
Mo, J. S. et al. Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway. Nat. Cell Biol. 17, 500–510 (2015).
Article CAS PubMed PubMed Central Google Scholar
Markmiller, S. et al. Context-dependent and disease-specific diversity in protein interactions within stress granules. Cell 172, 590–604 (2018).
Article CAS PubMed PubMed Central Google Scholar
Aulas, A. et al. Stress-specific differences in assembly and composition of stress granules and related foci. J. Cell Sci. 130, 927–937 (2017).
Article CAS PubMed PubMed Central Google Scholar
Jain, S. et al. ATPase-modulated stress granules contain a diverse proteome and substructure. Cell 164, 487–498 (2016).
Article CAS PubMed PubMed Central Google Scholar
Youn, J. Y. et al. High-density proximity mapping reveals the subcellular organization of mRNA-associated granules and bodies. Mol. Cell 69, 517–532 (2018).
Comments (0)