Analysis of FUS LLPS in Neurodegenerative Diseases

Fusion sarcoma (FUS) is a multifunctional RNA-binding protein of the FET family involved in stress granule formation and regulation of RNA processes. FUS has a high propensity for intrinsic self-assembly. Like TDP-43, FUS has an important role outside the nucleus of neurons. The researchers found that FUS undergoes liquid-liquid phase separation (LLPS) and further liquid-solid phase transformation when pathological cells form irreversible amyloid fibrils in response to environmental stress, associated with the development of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and polyglutamine diseases. However, the underlying mechanisms of this process remain unknown.

Fig. 1. Self-assembling model of FUS. (Boer EMJ, et al., 2020)

Customized Services

Like many other proteins, FUS can undergo LLPS both under artificial laboratory conditions and under natural conditions in vivo, resulting in the formation of liquid-like droplets containing ribonucleoprotein aggregates. Pathological and genetic analyses have also confirmed the association of FUS with a variety of neurodegenerative diseases. These neurodegenerative diseases can be avoided by preventing the persistent accumulation of FUS.

Here, CD BioSciences offers specialized services to analyze LLPS of FUS in neurodegenerative diseases. Our laboratory offers fluorescence recovery after photobleaching (FRAP), UV-Vis spectroscopy and microscopy combined with hydrostatic pressure changes to examine FUS LLPS, which can provide our clients with reliable data on FUS phase transition kinetics and phase reversibility.

Our technical team develops modulation strategies for FUS-focused intracellular LLPS, including:

• Modulation of FUS phase separation by physical stimulation
  We tuned the LLPS of FUS by changing environmental factors such as temperature, pressure, and light to alter intermolecular and intramolecular interactions, protein conformation, and module aggregation. This strategy is widely used to study the kinetics, mechanisms, and applications of FUS-LLPS condensates.
• Modulation of FUS phase separation by molecular modulators
  Molecular modulators can be involved in FUS condensation and thus affect protein-protein interactions. We offer cutting-edge techniques to analyze the modulation of FUS LLPS by a variety of molecular modulators, including 1,6-hexanediol, molecular chaperones, adenosine triphosphate (ATP), certain crowding agents, H⁺ /OH^-, nucleic acids, organic small molecules, and inorganic salts, etc.
• Modulation of the FUS phase behaviour by altering protein structures
  Post-translational modifications (PTMs) and amino acid sequence mutations are the switches of LLPS. We can analyze multiple PTMs of FUS, including phosphorylation, methylation and acetylation.

Furthermore, we systematically integrate these regulatory approaches with proteomic, transcriptomic, imaging, genetic, and epidemiological data to explore the pathogenesis of abnormal phase changes in FUS and to develop potential therapeutic targets to prevent and treat these neurodegenerative diseases.

CD BioSciences aims to analyze the regulation of FUS LLPS to develop potential therapeutic approaches for neurodegenerative diseases. If you are interested in our services, please feel free to contact us.