Phase separation and protein aggregation in neurodegenerative diseases
Biophysical Chemistry. 2026-11-01; 338: 107678
DOI: 10.1016/j.bpc.2026.107678
de La Seiglière H(1), Letourneur Æ(1), Ichas F(2), De Giorgi F(3).
Author information:
(1)SynTeam, Institut des maladies neurodégénératives, CNRS UMR5293, Univ.
Bordeaux, France.
(2)SynTeam, Institut des maladies neurodégénératives, CNRS UMR5293, Univ.
Bordeaux, France; Laboratory of Human Anatomy, DiSTeBA, University of Salento,
Lecce, Italy.
(3)SynTeam, Institut des maladies neurodégénératives, CNRS UMR5293, Univ.
Bordeaux, France. Electronic address: .
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.
Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.
DOI: 10.1016/j.bpc.2026.107678
PMID: 42418847
Conflict of interest statement: Declaration of competing interest The authors
declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this
paper.