Scientists have found a molecular switch of inflammation in Alzheimer's disease
Specialists from the Scripps Research Institute (Scripps Center) in the USA have discovered a hidden molecular mechanism that provokes chronic inflammation and destroys neural connections in Alzheimer's disease. This was reported on May 31 by Science Daily magazine.
In the course of the study, scientists identified a chemical change that puts the brain's immune system into hyperactivity mode. The focus was on the STING protein, which is normally responsible for early warning of threats. However, in Alzheimer's disease, it undergoes a modification known as S-nitrosylation (SNO).
Stuart Lipton, lead author of the study, Head of the Step Family Department at the Scripps Research Center and a clinical neurologist
This is a new and important therapeutic target for Alzheimer's disease. It is very interesting to see that blocking this mechanism in mice reduces inflammation and protects the very connections between brain cells that are lost in Alzheimer's disease, especially because we found activation of the same pathway in human brain samples with Alzheimer's disease and in models derived from human stem cells.
Scientists have determined that the reaction affects a specific component of the protein, cysteine-148. As soon as this site is modified, the STING begins to combine into large complexes that trigger the inflammatory process.
According to Lipton, the special feature of the target is the ability to suppress the pathological hyperactivation of the protein without disabling the normal immune response. He stressed that protein is still necessary for the body to protect against infections, so therapy is not aimed at blocking the entire molecule, but only at preventing its excessive activity.
Researchers have found high levels of altered protein (SNO-STING) in postmortem brain tissue samples from people with Alzheimer's disease. It also turned out that the accumulation of harmful proteins, such as amyloid beta, triggers a vicious circle: aggregates provoke inflammation, which leads to a modification of STING, which in turn further inflates the inflammatory process. The team is currently developing small molecules to block cysteine-148 and plans to begin their preclinical trials.
On May 28, Medical Xpress magazine linked blood biomarkers to the risk of developing Alzheimer's disease. According to the publication, such a connection was discovered for the first time. Experts emphasized that up to 40% of dementia cases can be delayed or prevented by eliminating risk factors such as physical and cognitive inactivity, depression, smoking, and heart health.
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