The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization
Open accessAbstract
Summary In amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), cytoplasmic aggregates of hyperphosphorylated TDP-43 accumulate and colocalize with some stressgranule components, but how pathological TDP-43 aggregation is nucleated remains unknown. In Drosophila, we establish that downregulation of Tankyrase, a poly (ADPribose) (PAR) polymerase, reduces TDP-43 accumulation in the cytoplasm and potently mitigates neurodegeneration. We establish that TDP-43 non-covalently binds to PAR via PAR-binding motifs embedded within its nuclear-localization sequence. PAR binding promotes liquid-liquid phase separation of TDP-43 in vitro and is required for TDP-43 accumulation in stress granules in mammalian cells and neurons. Stress-granule localization initially protects TDP-43 from disease-associated phosphorylation, but upon long-term stress, stress granules resolve leaving behind aggregates of phosphorylated TDP-43. Finally, small-molecule inhibition of Tankyrase in mammalian cells inhibits formation of cytoplasmic TDP-43 foci without affecting stress-granule assembly. Thus, Tankyrase inhibition antagonizes TDP-43-associated pathology and neurodegeneration and could have therapeutic utility for ALS/FTD.
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Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
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ImageJ2: ImageJ for the next generation of scientific image data
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A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation
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Liquid-Liquid Phase Separation in Biology
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Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling
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NPS@: Network Protein Sequence Analysis
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Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing
Alberti, S., & Hyman, A. A. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00326-6 · Cited by 1,160
Stress granules and neurodegeneration
Wolozin, B., & Ivanov, P. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0222-5 · Cited by 810
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis
Prasad, A., Bharathi, V., Sivalingam, V., Girdhar, A., & Patel, B. K. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00025 · Cited by 774
Properties of Stress Granule and P-Body Proteomes
Youn, J.-Y., Dyakov, B. J. A., Zhang, J., Knight, J. D. R., Vernon, R. M., Forman-Kay, J. D., & Gingras, A.-C. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.014 · Cited by 445
The role of liquid–liquid phase separation in aggregation of the TDP-43 low-complexity domain
Babinchak, W. M., Haider, R., Dumm, B. K., Sarkar, P., Surewicz, K., Choi, J.-K., & Surewicz, W. K. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.007222 · Cited by 396
Metadata
- Authors
- McGurk, L., Gomes, E., Guo, L., Mojsilovic-Petrovic, J., Tran, V., Kalb, R. G., Shorter, J., & Bonini, N. M.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 71
- Issue
- 5
- Pages
- 703-717.e9
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2887213234
- Cited by
- 409
- References
- 71
- FWCI
- 27.86
- Type
- journal article
- Language
- en
- Open access
- bronze
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- McGurk, L., Gomes, E., Guo, L., Mojsilovic-Petrovic, J., Tran, V., Kalb, R. G., Shorter, J., & Bonini, N. M. (2018). Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization. Molecular Cell. https://doi.org/10.1016/j.molcel.2018.07.002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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