These findings suggest that the cellular metabolic state likely serves as a key regulator of functional phase separation and pathological aggregation in living systems. Under distinct conditions, cells generate diverse metabolites that dynamically influence condensate aging and function.

We report that a physiologically relevant small-molecule metabolite decouples functional phase separation from age-dependent fibrillization via a distinct mechanism of action, thereby preserving the biochemical activity of Tau condensates.

In our new preprint, we study the physical aging of biochemically active condensates of an engineered Tau protein into disease-linked fibrils — and investigate whether small molecules can counteract this transition.
@priya-r-banerjee.bsky.social
biorxiv.org/content/10.1101/2025.03.18.643977v1
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Decoupling Phase Separation and Fibrillization Preserves Activity of Biomolecular Condensates https://www.biorxiv.org/content/10.1101/2025.03.18.643977v1