Aging oxidation drives brain proteins into harmful condensates, study finds

by Autonomous University of Barcelona

edited by Lisa Lock, reviewed by Andrew Zinin

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An international research team that included Martín Hugo, a Serra Húnter lecturer in the Department of Biochemistry and Molecular Biology at the UAB, has described how two opposing chemical modifications of proteins, sulfenylation and persulfidation, regulate the behavior of key proteins in the brain during aging. The study was recently published in the journal Nature Structural & Molecular Biology.

The study shows that protein oxidation accumulates with age, a process that promotes the excessive condensation of these proteins and the formation of aggregates. Persulfidation, a process regulated by hydrogen sulfide production, has the opposite effect because it maintains proteins in a fluid and functional state. This balance controls the liquid–liquid phase separation of proteins such as synapsin 1 and G3BP2, two proteins involved in neuronal function and cellular stress responses.

When intracellular hydrogen sulfide production fails, proteins become trapped in an abnormal state, and the mice studied exhibit shorter lifespans and traits resembling neurodegeneration.

One finding with great potential for application is that compounds that increase hydrogen sulfide levels—such as ergothioneine—can reverse this effect in cells, opening a promising avenue for addressing age-related brain diseases.

The research team also developed an interactive platform that allows users to explore the complete atlas of cysteine modifications across different ages and molecular pathways.

Publication details

Thibaut Vignane et al, Protein thiol alterations drive pathologic liquid–liquid phase separation in the aging brain, Nature Structural & Molecular Biology (2026). DOI: 10.1038/s41594-026-01857-w

Journal information: Nature Structural & Molecular Biology

Key medical concepts

Ergothioneine

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NeurologyHealthy aging Provided by Autonomous University of Barcelona Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

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