Reversibility and β-sheet formation are decoupled in tau condensate aging - PubMed
5 hours ago
- #biomolecular condensates
- #neurodegenerative diseases
- #tau protein
- Neurofibrillary tangles (NFTs) formed from tau protein are linked to cognitive decline in Alzheimer's disease.
- Tau aggregation involves biomolecular condensates that act as intermediates, transitioning into insoluble aggregates.
- The study maps tau's phase behavior, structural transitions, and thermodynamic reversibility during condensate aging.
- β-sheet enrichment and irreversible aggregation in tau occur at different rates and occupy distinct phase spaces, indicating they are mechanistically uncoupled.
- The research identifies β-sheet rich yet thermodynamically reversible tau condensate phases and irreversible intermediates lacking β-sheet structure.
- Findings expand the understanding of tau aggregation beyond a linear progression to fibrils, highlighting diverse intermediates with unique properties.
- The decoupling of structure and irreversibility in tau aggregation may offer new therapeutic targets.