Liquid-liquid Phase Separation and Inclusions of TDP-43

TDP-43 is a protein associated with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), limbic-predominant age-related TDP-43 encephalopathy (LATE) and, more generally, forms inclusions in many other neurodegenerative diseases. It is a complex protein formed by three structured domains and one intrinsically disordered C-terminal domain. It dimerizes and oligomerizes into functional species, but oligomerization can also be aberrant and lead to an uncontrolled, deleterious aggregation process. TDP-43 has indeed a peculiar self-assembly behavior as it can form oligomers, but also liquid droplets in vivo through a process known as liquid-liquid phase separation (LLPS), but eventually form neuronal cytoplasmic solid inclusions (NCIs), that may be amyloid or amorphous unstructured inclusions. The importance of LLPS in TDP-43 biology and its role in the ultimate process of NCI formation, as well as the nature of the ultimate NCIs associated with disease and responsible for them, are highly debated arguments.

This FASEB Catalyst Conference will bring together scientists to discuss the many unresolved and still debated issues on TDP-43 structure, biology, misbehavior, and involvement in diseases.

Organizer:
Fabrizio Chiti, PhD, Professor, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Italy

Registration Fee: $0