Liquid-liquid phase transitions and amyloid aggregation in proteins related to cancer and neurodegenerative diseases

Liquid-liquid phase separation (LLPS) and phase transition (LLPT) of proteins and nucleic acids have emerged as a new paradigm in cell biology. Here we will describe the recent findings about LLPS and LLPT, including the molecular and physical determinants leading to their formation, the resulting functions and their implications in cell physiology and disease. Amyloid aggregation is implicated in many neurodegenerative diseases and cancer, and LLPS of proteins involved in these diseases appear to be related to their function in different cell contexts. Amyloid formation would correspond to an irreversible liquid-to-solid transition, as clearly observed in the case of PrP, TDP43, FUS/TLS and tau protein in neurodegenerative pathologies as well as with the mutant tumor suppressor p53 in cancer. Nucleic acids play a modulatory effect on both LLPS and amyloid aggregation. Understanding the molecular events regulating how the demixing process advances to solid-like fibril materials is crucial for the development of novel therapeutic strategies against cancer and neurodegenerative maladies.