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Biomolecular condensates and disease pathogenesis.

Ke Ruan1, Ge Bai2,3, Yanshan Fang4,5

  • 1The First Affiliated Hospital & School of Life Sciences, Ministry of Education Key Laboratory for Membrane-less Organelles & Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China. kruan@ustc.edu.cn.

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Summary

Biomolecular condensates, formed by liquid-liquid phase separation (LLPS), compartmentalize cells. Aberrant LLPS is linked to diseases, but new methods and chemical modulators offer therapeutic potential.

Keywords:
biomolecular condensateliquid-liquid phase separationmembraneless organelle

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Area of Science:

  • Cell biology
  • Biochemistry
  • Molecular medicine

Background:

  • Biomolecular condensates, or membraneless organelles (MLOs), are crucial for cellular organization, formed via liquid-liquid phase separation (LLPS).
  • Dysregulation of LLPS and MLOs is implicated in various pathologies, including neurodegeneration and cancer.

Purpose of the Study:

  • To review methods for monitoring LLPS.
  • To discuss MLO biogenesis and function.
  • To highlight the role of phase separation disruption in diseases and the potential of chemical modulators.

Main Methods:

  • Literature review of LLPS monitoring techniques.
  • Analysis of MLO formation, function, and disease association.
  • Exploration of chemical modulators targeting phase separation.

Main Results:

  • Progress in developing methods to monitor phase separation is summarized.
  • Disruption of phase separation homeostasis is observed in neurodegenerative disorders, hearing loss, cancers, and immunological diseases.
  • Emerging chemical modulators of phase separation show therapeutic promise.

Conclusions:

  • Understanding LLPS and MLOs is critical for comprehending cellular function and disease.
  • Targeting phase separation represents a novel therapeutic strategy for a range of pathological conditions.