Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation

Significance Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. Although dysregulated hydrogen sulfide (H 2 S) metabolism has been reported in AD, and H 2 S donors are beneficial, molecular mechanisms underlying neuroprotective effects of H 2 S are largely unknown. We now show that H 2 S confers neuroprotection by sulfhydrating GSK3β to inhibit its activity, thereby preventing hyperphosphorylation of Tau, a key pathogenic event in AD. Administering H 2 S donors improves motor and cognitive functions in a mouse model of AD.