Language
English
Publication Date
4-10-2026
Journal
Biomolecules
DOI
10.3390/biom16040560
PMID
42072681
PMCID
PMC13114259
PubMedCentral® Posted Date
4-10-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Neurodegenerative diseases arise when normally functional aggregation-prone proteins transition into stable cross-β amyloid fibrils. Although these fibrils share a conserved architecture, the pathways that lead to fibrillation vary across proteins and cellular environments. Liquid-liquid phase separation is now recognized as a central organizer of intracellular biochemistry that modulates protein aggregation. Physiological condensation can buffer aggregation by maintaining macromolecular solubility and providing partner interactions that compete against pathological protein-protein interactions. However, condensates can transform and age into gel-like states that can favor the emergence of β-rich oligomers and solid-state fibrils. Across six disease-linked proteins that include Tau, α-synuclein, amyloid-β, TDP-43, FUS, and hnRNPA1, we compare how sequence-encoded interaction motifs, cellular cofactors, and interfacial microenvironments shape the balance between physiological condensates and pathological amyloids. Here, we highlight the unifying drivers of aggregation and intervention points that preserve native function while limiting toxic amyloid formation.
Keywords
Humans, Neurodegenerative Diseases, alpha-Synuclein, Amyloid, Amyloid beta-Peptides, DNA-Binding Proteins, tau Proteins, Heterogeneous Nuclear Ribonucleoprotein A1, RNA-Binding Protein FUS, Protein Aggregation, Pathological, Animals, Biomolecular Condensates, neurodegeneration, biomolecular condensates, fibrillation, amyloids, Tau, α-synuclein, amyloid-β, TDP-43, FUS, hnRNPA1
Published Open-Access
yes
Recommended Citation
Lathan Lucas, Josephine C Ferreon, and Allan Chris M Ferreon, "Condensate State as Determinant of Amyloid Pathology in Neurodegeneration" (2026). Faculty, Staff and Students Publications. 8031.
https://digitalcommons.library.tmc.edu/baylor_docs/8031