A sulfur switch decides when ageing brain proteins clump

An international team including Martín Hugo of the Universitat Autònoma de Barcelona reported in Nature Structural & Molecular Biology on 13 September 2026 that two opposing chemical modifications of protein cysteines decide whether brain proteins stay dispersed or condense.

Thiol oxidation, which accumulates with age, promotes the formation of biomolecular condensates. Persulfidation — governed by the cell’s production of hydrogen sulfide — does the reverse, holding the same proteins in a fluid, working state. Two proteins carry the consequence: synapsin 1, which regulates neurotransmitter release, and G3BP2, which assembles and dissolves stress granules. Mice unable to make enough hydrogen sulfide had shorter lifespans and traits resembling neurodegeneration. Ergothioneine, a compound that raises hydrogen sulfide levels, reversed the excess condensation in cells.

The claim is mechanistic and the evidence is in mice and cultured cells, with no human data. What makes it worth recording is the shape of the target: not a protein to remove, but a chemical state to maintain, on proteins the brain needs to keep working rather than clear away.