Liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a rapidly emerging field of study, aimed at understanding the process of biomolecular condensate formation and its role in cellular functions. LLPS has been shown to be responsible for the generation of promyelocytic leukemia protein bodies, stress granules, and intrinsically disordered protein condensates.
Recently, it has been discovered that different neurodegenerative disease-related proteins, such as alpha-synuclein and amyloid-beta are capable of forming heterotypic droplets. Other reports have also shown non-LLPS cross interactions between various amyloidogenic proteins and the resulting influence on their amyloid fibril formation. Combined, these observations suggest that protein interactions during LLPS and heterotypic droplet formation may be a critical step in the onset of neurodegenerative diseases.
This work will be dedicated towards examining the cross-interaction between neurodegenerative disease-related proteins during LLPS and how the process of heterotypic droplet formation influences their amyloid aggregation and resulting fibrillar structures.