查看文章

Aggregation of the RNA binding protein TDP-43 (TAR DNA-binding protein 43) is a common pathological hallmark shared by several age-related neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The predominantly nuclear TDP-43 normally undergoes liquid-liquid phase separation (LLPS), in which a homogeneous solution separates into two compartments resembling oil droplets in vinegar.

Intranuclear TDP-43 can phase-separate under physiological conditions. Cellular stress can induce cytoplasmic TDP-43 liquid droplets, which can transition to a solid state, suggesting that TDP-43 aggregation observed in neurodegeneration could be initiated by LLPS. The mechanisms that drive phase separation and aggregation remain unclear.

We identified key regulatory mechanisms of TDP-43 phase separation in …