Cited by 28Alzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis ResearchRNA Research and Splicing

Tau liquid–liquid phase separation: At the crossroads of tau physiology and tauopathy

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Islam, Majedul, Shen, Fengyun, Regmi, Deepika, Petersen, Katherine, Karim, Md Raza Ul, Du, Deguo·2024·Journal of Cellular Physiology

Abstract

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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Crossref · 10.1002/jcp.30853

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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
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
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

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