Abnormal aggregates of tau, a protein found in the brain, are one of the defining characteristics of Alzheimer’s disease. These aggregates, known as tau tangles, inhibit normal brain function. The degree of cognitive impairment in Alzheimer’s disease is correlated with their presence. Findings from a new study suggest that hydrogen sulfide prevents tau tangle formation by inhibiting tau phosphorylation.
Hydrogen sulfide is a naturally occurring gas, notable for its strong odor of rotten eggs. Exposure to hydrogen sulfide can cause irritation to the eyes and respiratory system. Hydrogen sulfide is also produced in the body’s tissues. Sometimes referred to as a gasotransmitter, it serves as a signaling molecule and actively participates in regulation of a wide range of physiological functions, including inflammation and cell death. Evidence suggests that hydrogen sulfide inhibits free radical reactions in aging and age-related neurodegenerative diseases. Hydrogen sulfide signaling is impaired with aging.
Tau phosphorylation is a chemical modification facilitated by the activity of several enzymes, including glycogen synthase kinase 3-beta (GSK3-beta). Hyperactive GSK3-beta promotes abnormal tau phosphorylation and subsequent tangle formation.
The investigators used a mouse model of Alzheimer’s disease to study the effects of hydrogen sulfide on the brain. They injected the mice with hydrogen sulfide daily for 12 weeks and then subjected the mice to various cognitive and motor tests. They also conducted biochemical experiments to gauge the effects of hydrogen sulfide on GSK3-beta.
The tests revealed that the mice treated with hydrogen sulfide performed 50 percent better on the tests than mice that did not receive the treatment. The biochemical experiments revealed that a chemical modification of GSK3-beta called sulfhydration inhibits tau phosphorylation. However, under conditions of low hydrogen sulfide levels, GSK3-beta is disproportionately attracted to tau, promoting hyperphosphorylation and tau tangle formation.
These findings suggest that strategies to improve hydrogen sulfide status in the brain show promise as a treatment for Alzheimer’s disease.
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