Prion-Like Proteins in Phase Separation and Their Link to Disease

• Main Authors: Macy L. Sprunger, Meredith E. Jackrel
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Biomolecules
• Subjects: prions; prion-like domains; amyloid; protein misfolding; liquid-liquid phase separation; aberrant phase transitions
• Online Access: https://www.mdpi.com/2218-273X/11/7/1014

Aberrant protein folding underpins many neurodegenerative diseases as well as certain myopathies and cancers. Protein misfolding can be driven by the presence of distinctive prion and prion-like regions within certain proteins. These prion and prion-like regions have also been found to drive liquid-liquid phase separation. Liquid-liquid phase separation is thought to be an important physiological process, but one that is prone to malfunction. Thus, aberrant liquid-to-solid phase transitions may drive protein aggregation and fibrillization, which could give rise to pathological inclusions. Here, we review prions and prion-like proteins, their roles in phase separation and disease, as well as potential therapeutic approaches to counter aberrant phase transitions.