Tau liquid–liquid phase separation: At the crossroads of tau physiology and tauopathy
Open accessAbstract
Abnormal deposition of tau in neurons is a hallmark of Alzheimer's disease and several other neurodegenerative disorders. In the past decades, extensive efforts have been made to explore the mechanistic pathways underlying the development of tauopathies. Recently, the discovery of tau droplet formation by liquid–liquid phase separation (LLPS) has received a great deal of attention. It has been reported that tau condensates have a biological role in promoting and stabilizing microtubule (MT) assembly. Furthermore, it has been hypothesized that the transition of phase‐separated tau droplets to a gel‐like state and then to fibrils is associated with the pathology of neurodegenerative diseases. In this review, we outline LLPS, the structural disorder that facilitates tau droplet formation, the effects of posttranslational modification of tau on condensate formation, the physiological function of tau droplets, the pathways from droplet to toxic fibrils, and the therapeutic strategies for tauopathies that might evolve from toxic droplets. We expect a deeper understanding of tau LLPS will provide additional insights into tau physiology and tauopathies.
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Tau has an intrinsic propensity to undergo liquid-liquid phase separation.
“Tau, a protein involved in several neurodegenerative diseases, has an intrinsic propensity to undergo liquid–liquid phase separation (LLPS) [55,56,57].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [55]
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- Authors
- Islam, M., Shen, F., Regmi, D., Petersen, K., Karim, M. R. U., & Du, D.
- Affiliations
- Florida Atlantic University (US)
- Corresponding author
- Islam, Majedul
- Du, Deguo
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2022-08-18
- Volume
- 239
- Issue
- 6
- Pages
- e30853-e30853
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- PMC
- PMC9938090
- OpenAlex
- W4292230259
- Cited by
- 28
- References
- 160
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 7 · 2022: 2
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R15GM116006)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- tau protein, liquid-liquid phase separation, tauopathy, Alzheimer's disease, microtubule assembly, post-translational modification, neurodegeneration, treatment options
- MeSH terms
- Phase Separation, Alzheimer Disease, Animals, Humans, Microtubules, Protein Conformation, Protein Processing, Post-Translational, Stress, Physiological, tau Proteins, Tauopathies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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