New Paper - A26 Alberti
24.07.2025
New publication from Simon Alberti´s group
The paper by Simon and colleagues identifies a multi-step mechanism by which the RNA-binding protein TDP-43 forms pathological aggregates within stress granules, RNA-rich biomolecular condensates, in the neurodegenerative diseases amyotrophic lateral sclerosis. Aggregation requires local up-concentration of TDP-43 beyond a critical threshold combined with oxidative stress, triggering intra-condensate demixing and a subsequent liquid-to-solid transition. Blocking oxidation-dependent demixing abolishes aggregation in cells and disease models. More broadly, the study highlights how RNA-rich condensates act as crucibles that concentrate RNA-binding proteins to pathological thresholds. This concept parallels nucleic acid immunity, where condensation and compartmentalization of nucleic acids and their sensors shape signaling outcomes, illustrating how dysregulated nucleic-acid–driven condensation can convert protective stress responses into chronic pathology.
Published in Cell: Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates
