Commonly identified as toxic, corrosive and the smell of rotten eggs, the reputation of hydrogen sulfide may soon gain a facelift thanks to Johns Hopkins Medicine researchers. In experiments in mice, researchers have shown that the gas with a false odor may help protect aging brain cells against Alzheimer’s disease. The discovery of the biochemical reactions that make this possible opens doors to the development of new drugs to combat neurodegenerative disease.
The results of the study are reported in the journal Jan. 11 den Proceedings of the National Academies of Science.
“Our new data strongly link cell age, neurodegeneration and signaling using hydrogen sulfide and other gaseous molecules within the cell,” said Bindu Paul, M.Sc., Ph.D., faculty research professor in neuro-science in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine and a corresponding lead author on the study.
The human body naturally produces small levels of hydrogen sulfide to help regulate activities throughout the body, from cell metabolism to dilation of blood vessels. The rapidly increasing field of gasotransmission indicates that gases are the major cell messenger molecules, especially important in the brain. However, unlike conventional neurotransmitters, gases cannot be stored in cells.
Thus, gases work through different means to enable fast cellular messaging. In the case of hydrogen sulfide, this involves the modification of target proteins by a process called chemical sulfhydration, which alters their activity, says Solomon Snyder, D.Phil., D.Sc., MD, senior professor of neuroscience at Johns Hopkins University School of Medicine and a corresponding author of the study.
Studies using a new method have shown that levels of sulfhydration in the brain decrease with age, a trend that is increased in patients with Alzheimer’s disease. “Here, using the same method, we are now confirming a decrease in sulfhydration in the AD brain,” said colleague Milos Filipovic, Ph.D., principal investigator, Leibniz-Institut für Wissenschaften Analytics – ISAS.
For the current research, Johns Hopkins Medicine scientists studied mice that were genetically engineered to mimic human Alzheimer’s disease. They introduced the mice with a hydrogen sulfide-carrying fertilizer called NaGYY, developed by their colleagues at the University of Exeter in the United Kingdom, which releases molecular hydrogen sulfide molecules. as they travel 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 mental and motor activity by 50% compared to mice that did not receive the injections of NaGYY. Treated mice had better memory of the platforms where platforms were present and appeared more physically active than their untreated peers with Alzheimer’s-like disease.
The results showed that the behavioral results of Alzheimer’s disease could be reversed by the ingestion of hydrogen sulfide, but the researchers wanted to study how the brain chemically responded to the gaseous molecules.
A series of biochemical tests revealed a conversion to a common enzyme called glycogen synthase β (GSK3β). In the presence of healthy levels of hydrogen sulfide, GSK3β usually acts as a signaling molecule, adding chemical signals to other proteins and altering their action. However, the researchers found that if hydrogen sulfide is not present, GSK3β is transferred to another protein in the brain called Tau.
When GSK3β interacts with Tau, Tau changes to a form that collapses and collapses within zero cells. As Tau nodules grow, the tight proteins block communication between nerves, eventually causing them to die. This leads to a decline and eventual loss of psychology, memory and motor function that is normal for Alzheimer’s disease.
Understanding event prevention is important for the design of treatments that prevent this interaction as hydrogen sulfide is capable of. “
Daniel Giovinazzo, MD / Ph.D. Student, First Author of the Study
Until recently, researchers did not have the tools of pharmaceutical devices to visualize how the body slowly produces small amounts of hydrogen sulfide inside cells. “The fertilizer used in this study does just that and shows that by correcting brain levels of hydrogen sulfide, we could reverse some aspects of Alzheimer’s disease,” says co. study worker Matt Whiteman, Ph.D., experimental therapeutic professor at the University of Exeter School of Medicine.
The Johns Hopkins Medicine team and their international colleagues plan to continue to study how sulfa groups interact with GSK3β and other proteins involved in the pathogenesis of Alzheimer’s disease in cell and organ systems. other. The team also plans to test hydrogen sulfide delivery molecules as part of their ongoing campaign.