Related Experiment Video
Updated: Aug 5, 2026
09:35
Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain
Published on: October 24, 2017
Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain
Thibaut Vignane1,2, Martín Hugo3,4, Christian Hoffmann5
1Leibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany. vignane@med.uni-frankfurt.de.
Nature Structural & Molecular Biology
|July 30, 2026
Summary
Aging disrupts cellular protein regulation, leading to disease. Protein persulfidation, a process involving hydrogen sulfide, can reverse this, potentially treating age-related conditions.
Area of Science:
- Biochemistry
- Molecular Biology
- Aging Research
Background:
- Cellular homeostasis depends on protein post-translational modifications (PTMs) and biomolecular condensation.
- Aging disrupts these processes, increasing disease risk and mortality.
Purpose of the Study:
- To investigate the role of cysteine PTMs in age-related changes in biomolecular condensation.
- To explore the therapeutic potential of protein persulfidation in mitigating aging effects.
Main Methods:
- Chemoproteomic techniques to map cysteine PTMs in the mouse brain.
- Analysis of protein phase separation properties (synapsin 1, G3BP2).
- Assessment of lifespan and protein aggregation in mice deficient in cystathionine γ-lyase.
Main Results:
- Age-related thiol oxidation promotes biomolecular condensate formation.
- Protein persulfidation inhibits condensation, preserving protein function.
- Altered PTMs impair neurotransmitter release and stress granule dynamics, mimicking aging phenotypes.
- Hydrogen sulfide deficiency shortens lifespan and causes age-related protein aggregates.
Conclusions:
- Age-induced PTM alterations dysregulate biomolecular condensation.
- Protein persulfidation offers a therapeutic strategy to reverse these changes.
- Sulfide donors may help manage age-related diseases.
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