Work

Understanding liquid–liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation

Year: 2026

Type: article

Abstract: Phase separation is an important process in biology associated with formation of membraneless organelles but possibly related to the emergence of solid inclusions. TDP-43 is a largely studied paradigmatic case, as it forms neuronal cytoplasmic inclusions in neurodegenerative diseases and is an essential component of many membraneless organelles. Here, we review the physicochemical fundamentals of liquid-liquid phase separation (LLPS) of TDP-43 and its fragments in vitro, showing that full-length TDP-43 requires RNA or chaperones to form stable liquid droplets. We describe TDP-43-containing membraneless organelles and the debate on whether these assemblies represent reservoirs for pathological solid inclusion formation.

Source: Genome biology

DOI: 10.1186/s13059-026-03956-9

Authors: Alessandra Bigi, Fabrizio Chiti

Institution: University of Florence

Language: English

Topic: Amyotrophic Lateral Sclerosis Research

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,490