Multiscale simulations reveal molecular dynamics of TDP-43 assemblies

Abstract

The RNA binding protein TDP-43 is involved with mRNA processing and transport from the nucleus to the cytoplasm. TDP-43 localizes in the nucleus as well as accumulates in cytoplasmic intracellular condensates and stress granules. Aggregation and formation of amyloid-like fibrils of cytoplasmic TDP-43 are hallmarks of numerous neurodegenerative diseases, most strikingly present in >90% of amyotrophic lateral sclerosis (ALS) patients. How excessive accumulation of cytoplasmic TDP-43 causes, or is caused by, neurodegeneration is presently not known.