The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
The role of liquid–liquid phase separation in aggregation of the TDP-43 low-complexity domain
Open accessAbstract
Pathological aggregation of the transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with several neurodegenerative disorders, including ALS, frontotemporal dementia, chronic traumatic encephalopathy, and Alzheimer's disease. TDP-43 aggregation appears to be largely driven by its low-complexity domain (LCD), which also has a high propensity to undergo liquid-liquid phase separation (LLPS). However, the mechanism of TDP-43 LCD pathological aggregation and, most importantly, the relationship between the aggregation process and LLPS remains largely unknown. Here, we show that amyloid formation by the LCD is controlled by electrostatic repulsion. We also demonstrate that the liquid droplet environment strongly accelerates LCD fibrillation and that its aggregation under LLPS conditions involves several distinct events, culminating in rapid assembly of fibrillar aggregates that emanate from within mature liquid droplets. These combined results strongly suggest that LLPS may play a major role in pathological TDP-43 aggregation, contributing to pathogenesis in neurodegenerative diseases.
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Cites
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
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A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation
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Tau protein liquid–liquid phase separation can initiate tau aggregation
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Alberti, S., & Hyman, A. A. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00326-6 · Cited by 1,160
Phase separation and neurodegenerative diseases: a disturbance in the force
Zbinden, A., Pérez-Berlanga, M., De Rossi, P., & Polymenidou, M. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.09.014 · Cited by 500
Disease‐linked TDP‐43 hyperphosphorylation suppresses TDP‐43 condensation and aggregation
Gruijs da Silva, L. A., Simonetti, F., Hutten, S., Riemenschneider, H., Sternburg, E. L., Pietrek, L. M., Gebel, J., Dötsch, V., Edbauer, D., Hummer, G., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021108443 · Cited by 192
Surface electrostatics govern the emulsion stability of biomolecular condensates
Welsh, T. J., Krainer, G., Espinosa, J. R., Joseph, J. A., Sridhar, A., Jahnel, M., Arter, W. E., Saar, K. L., Alberti, S., Collepardo-Guevara, R., et al. (2020) · doi:10.1101/2020.04.20.047910 · Cited by 168
Liquid-liquid phase separation in Alzheimer’s disease
Fu, Q., Zhang, B., Chen, X., & Chu, L. (2024) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02407-3 · Cited by 33
Metadata
- Authors
- Babinchak, W. M., Haider, R., Dumm, B. K., Sarkar, P., Surewicz, K., Choi, J.-K., & Surewicz, W. K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 294
- Issue
- 16
- Pages
- 6306-6317
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2916646997
- Cited by
- 396
- References
- 67
- FWCI
- 22.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Babinchak, W. M., Haider, R., Dumm, B. K., Sarkar, P., Surewicz, K., Choi, J.-K., & Surewicz, W. K. (2019). The role of liquid–liquid phase separation in aggregation of the TDP-43 low-complexity domain. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.ra118.007222
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