Posted on 14 January 2021
Hydrogen sulphide isn’t exactly a substance you want to spend time around. Perhaps best known for its foul rotten egg smell, hydrogen sulphide is a poisonous, corrosive and flammable gas. However, it also happens to play an important role in the human body, where it can be synthesised by cells to act as a signalling molecule. Hydrogen sulphide signalling is implicated in ageing and cognition.
Previous research has suggested that decline in hydrogen sulphide signalling in the brain during ageing contributes to the development of Alzheimer’s disease. In this research, scientists present their findings that hydrogen sulphide can be used to treat Alzheimer’s disease in mice.
For the current research, the Johns Hopkins Medicine scientists studied mice genetically engineered to mimic human Alzheimer’s disease. They injected the mice with a hydrogen sulfide-carrying compound called NaGYY, developed by their collaborators at the University of Exeter in the United Kingdom, which slowly releases the passenger hydrogen sulfide molecules while traveling throughout the body. The researchers then tested the mice for changes in memory and motor function over a 12-week period.
Behavioral tests on the mice showed that hydrogen sulfide improved cognitive and motor function by 50% compared with mice that did not receive the injections of NaGYY. Treated mice were able to better remember the locations of platform exits and appeared more physically active than their untreated counterparts with simulated Alzheimer’s disease.
The researchers also investigated the mechanism behind the effects of hydrogen sulfide.
A series of biochemical experiments revealed a change to a common enzyme called glycogen synthase β (GSK3β). In the presence of healthy levels of hydrogen sulfide, GSK3β typically acts as a signalling molecule, adding chemical markers to other proteins and altering their function. However, the researchers observed that in the absence of hydrogen sulfide, GSK3β is over attracted to another protein in the brain called Tau.
When GSK3β interacts with Tau, Tau changes into a form that tangles and clumps inside nerve cells. As Tau clumps grow, the tangled proteins block communication between nerves, eventually causing them to die. This leads to the deterioration and eventual loss of cognition, memory and motor function that is characteristic of Alzheimer’s disease.
The main challenge in using hydrogen sulphide therapeutically has been finding a delivery method that mimics normal signalling in the body, as living cells only produce hydrogen sulphide in tiny quantities at a time. NaGYY now provides such a delivery method.
It’s still far too early to say whether this approach could be used to treat Alzheimer’s disease in humans, however. Successes in animal models haven’t historically translated well into humans where neurodegenerative diseases are concerned, so human trials will be needed before we start to get a good idea as to whether hydrogen sulphide could be an effective treatment.