TDP-43 forms cytoplasmic aggregates in degenerating neurons of frontotemporal dementia (FTD) patients. Laferrière et al. now establish that TDP-43 assemblies from distinct FTD subtypes have different structures, neurotoxicities, and seeding activities, which correlate with FTD severity. Thus, distinct pathological TDP-43 assemblies akin to prion strains might underpin distinct FTD subtypes.
References
Guo, L. & Shorter, J. Cold Spring Harb. Perspect. Med. 7, a024554 (2017).
Neumann, M. et al. Science 314, 130–133 (2006).
Collinge, J. & Clarke, A. R. Science 318, 930–936 (2007).
Shorter, J. Mol. Biosyst. 6, 1115–1130 (2010).
King, O. D., Gitler, A. D. & Shorter, J. Brain Res. 1462, 61–80 (2012).
Ayers, J. I. & Cashman, N. R. Handb. Clin. Neurol. 153, 337–354 (2018).
Nonaka, T. & Hasegawa, M. Cold Spring Harb. Perspect. Med. https://doi.org/10.1101/cshperspect.a024463 (2018).
Laferrière, F. et al. Nat. Neurosci. https://dx.doi.org/10.1038/s41593-018-0294-y (2018).
Becker, L. A. et al. Nature 544, 367–371 (2017).
Guo, L. et al. Cell 173, 677–692.e20 (2018).
Shorter, J. Curr. Opin. Genet. Dev. 44, 1–8 (2017).
McGurk, L. et al. Mol. Cell 71, 703–717.e9 (2018).
McGurk, L. et al. Acta Neuropathol. Commun. 6, 84 (2018).
Vogler, T.O. et al. Nature https://doi.org/10.1038/s41586-018-0665-2 (2018).
Porta, S. et al. Nat. Commun. 9, 4220 (2018).
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Barbieri, E.M., Shorter, J. TDP-43 shapeshifts to encipher FTD severity. Nat Neurosci 22, 3–5 (2019). https://doi.org/10.1038/s41593-018-0299-6
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DOI: https://doi.org/10.1038/s41593-018-0299-6
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