Phase separation and protein aggregation in neurodegenerative diseases.

Authors

Hortense de La Seiglière, Ænora Letourneur, François Ichas, Francesca De Giorgi

Published in

Biophysical chemistry. Volume 338. Pages 107678. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

Neurodegenerative diseases such as Alzheimer's, Parkinson's, frontotemporal dementia, and ALS are characterized by amyloid protein aggregation involving intrinsically disordered proteins that are also capable of liquid-liquid phase separation (LLPS). LLPS, known to drive the formation of dynamic membraneless organelles essential for cellular functions, can play a role in limiting fibrillation process or aberrantly transition into solid aggregates under pathological conditions. Here we review how mutations, post-translational modifications, and environmental factors can modulate LLPS of proteins like Tau, TDP-43, FUS, and α-synuclein, potentially regulating amyloid aggregation. We also examine the interplay of these proteins exploring how LLPS and condensate maturation could impinge on the emergence of co-pathologies contributing to disease progression. Finally we discuss emerging therapeutic strategies, aimed at modulating phase separation dynamics.

PMID:
42418847
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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