What is it about?

Hydrogen sulfide donors prevent cognitive and motor decline in mouse models of Alzheimer's disease. One of the ways by which the gas is protective is by modifying glycogen synthase kinase beta and inhibiting its activity. This prevents excessive phosphorylation of Tau and neurotoxicity. The modification elicited by hydrogen sulfide is called persulfidation/sulfhydration, where the -SH groups of reactive cysteine residues on proteins are converted to -SSH groups. In doing so, hydrogen sulfide can modulate protein function. Sulfhydration is decreased in both mouse models of AD as well as human AD. Administering hydrogen sulfide donors rescues this diminished sulfhydration in the 3xTg-AD mouse model of AD. Interestingly, foods such as garlic have precursors of hydrogen sulfide, which may explain some of their beneficial effects.

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Why is it important?

Alzheimer's disease is the leading cause of dementia in the elderly. Currently, there is no cure for the disease. Thus there is an unmet need for development of novel therapeutics.


A vast majority of AD cases are sporadic, thus it is clear that there are several, as yet unidentified, pathways operating. Although hydrogen sulfide was shown to be neuroprotective in AD, molecular mechanisms underlying protection were not well characterized. It was a pleasure elucidating one of the signaling pathways regulated by the gas in a study involving multiple laboratories. The study involved multidisciplinary expertise to approach the problem from various angles. It is very likely that hydrogen sulfide also modulates additional neuroprotective cascades and we are in the process of identifying them.

Bindu Paul
Johns Hopkins University

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This page is a summary of: Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation, Proceedings of the National Academy of Sciences, January 2021, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2017225118.
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