Protein aggregation reduces the elasticity of blood vessels in the brain

Reviewed by Emily Henderson, B.Sc.September 9, 2020

Protein deposits called “medins” appear in almost all older people and reduce the elasticity of blood vessels during aging and thus can be a risk factor for vascular dementia. Report in a scientific journal by experts from the German Center for Neurodegenerative Diseases (DZNE) and the University of Tubingen’s Hearty Institute Brain Research (HIH) PNAS.. Researchers view these deposits as targets for future treatments. Their findings are based on studies in mice and analysis of human tissue samples.

Almost everyone over the age of 50 is known to have a small mass of the protein Medin on their walls.

These deposits are clearly a side effect of the aging process. They are found primarily in upper body vessels, including the aorta and cerebral vessels. Most surprisingly, our study was able to detect Medin particles not only in brain tissue samples of deceased individuals, but also in old mice, despite the limited lifespan of these animals. .. ”

Dr. Jonas Neher, current research director, Tubingensite at DZNE and scientist at HIH

Medin is considered problematic because it belongs to a group of molecules called “amyloids” that are often associated with pathological conditions. A prominent example is “amyloid beta”, whose aggregates are involved in Alzheimer’s disease. “It has long been hypothesized that Medin aggregates could have a negative effect on blood vessels and contribute to vascular disease. Recent studies support this hypothesis. Results from these previous findings According to the report, elderly people with vascular dementia should be healthy individuals.”

Blunt ship

However, despite these suspicious signs, there is still no conclusive evidence that protein masses are actually harmful. The research team led by Neher has succeeded in proving this. This was made possible by the discovery that Medin deposits form in aged mice. Their work is the result of collaborative work with scientists from Frankfurt, Munich, Liverpool and London.

“We investigated how fast blood vessels in the brain could dilate. To do this, we compared aged mice with meditin deposits with mice that were genetically deficient in meditin and therefore did not develop meditin deposits,” Nier said. Said. “Almost all older people have aggregates of medins, so it’s almost impossible to compare people of almost the same age with or without aggregates,” he explained.

Neher’s team, like humans, observed that mice show increasing amounts of Medin particles in blood vessels with age. “In this respect, the mouse seems to mimic the human situation properly,” Neher said.

In mice, the researchers also found that blood vessels with Medin deposition expand more slowly than blood vessels without Medin when the brain is active and requires a higher blood supply. “Cerebrovascular vessels with medins appear to be less flexible and less responsive.” However, the ability of blood vessels to expand rapidly helps regulate blood flow and provide the brain with an optimal supply of oxygen and nutrients. The researchers said it was important. “If this ability is compromised, it can have far-reaching effects on organ function.” Therefore, medin deposits appear to contribute to poor vascular function in old age. “And this is probably not just the case in the brain, because deposits can also spread to other blood vessels and thus lead to cardiovascular disease as well as vascular dementia.”

Neher cannot give a definitive answer about how Medin particles act on blood vessels. But he has the theory: “Fibers run in the walls of blood vessels that allow the blood vessels to expand and contract. Because protein deposits are embedded in the walls of the blood vessels, they interfere with the function of these elastic fibers. There is a possibility.”

Therapeutic target

Medin is derived in a yet unknown way, especially from the large proteins involved in the formation of new blood vessels. “If this precursor molecule could be stabilized by drugs, it could regulate the production of medins, or it might stimulate the degradation of medin aggregates, which could affect the blood vessels and brain of the elderly. It may help you stay healthy, but such drugs are available to date”. “So it’s important to see medins as a risk factor that almost every elderly person carries within them. Medins really affect a large number of people, but so far have received little attention in therapeutic research. Hmm. Please get more spotlight.”