A research team from the Medical University of South Carolina (MUSC)driven by Hongkuan Fanassociate professor in the Department of Pathology and Laboratory Medicine, found that by blocking or inhibiting the action of Fli-1 in a mouse model with Alzheimer’s disease, the memory of the mice improved. The genesis of this intuition is due to the study of the dangers, cells that are less present in the brain tissue of patients who died from Alzheimer’s.
However, scientists also found higher values of Fli-1, a protein found more often in blood cells and thought to govern their development. Hence the attempt to try to inhibit the protein which also prevented immune cells from entering the brain and causing the inflammation that is a hallmark of Alzheimer’s disease. Blocking Fli-1 could be a promising new approach for treating Alzheimer’s disease and other dementias.
Alzheimer’s disease is a problem that is worsening over time, with the aging of the population, it will reach exponential figures. According to the Alzheimer’s Association, more than 6 million Americans have been affected by Alzheimer’s disease and 1 in 3 elderly people will die. By 2050, the cost of Alzheimer’s disease, currently estimated at $ 355 billion, will rise to $ 1.1 trillion.
The results of the Research scientists from the Medical University of South Carolina were published in the scientific journal Molecular Therapy.
Inhibiting FLI-1: Some insights into research
“We are really excited about these data because they suggest that Fli-1 could be a new therapeutic target for Alzheimer’s.“, Said the professor Hongkuan Fanat the head of the research: “Better treatments for Alzheimer’s disease are urgently needed. Most existing Alzheimer’s treatments simply treat the symptoms and do little to address the underlying causes.“.
The scientific community has long been aware that people with vascular problems, or problems with the heart or blood vessels, are at greater risk of developing Alzheimer’s disease and other dementias. These include people who have had a heart attack or who have diabetes or high blood pressure or cholesterol.
This information should come as no surprise, as the brain is starved for oxygen. When he doesn’t get enough of it because his blood flow is inadequate, his cells don’t work well and can start dying. The dangers that line the walls of tiny blood vessels known as capillaries ensure that the brain’s energy and waste disposal demands are met.
“The capillary is where all the action is“, he has declared Perry HalushkaMD, Ph.D., distinguished university professor of cellular and molecular pharmacology. “It’s where all these exchanges really happen.”
Pericytes also help build the blood brain barrier that prevents impurities and immune cells in the blood from reaching the brain. They also help remove beta amyloid, known to be a culprit in Alzheimer’s disease, from the brain.
When pericytes are lost, immune cells and impurities begin leaking into the brain, causing it to become inflamed and ultimately leading to cell death and decline in mental function.
“Pericytes can play a much more important role in dementia than was initially thought“Said Halushka. “This is especially true in the aging population, where vascular dementia will become a bigger problem ”.
The MUSC team examined the brains of people who died of Alzheimer’s, using the resources of the brain bank of the Carroll A. Campbell, Jr. Neuropathology Laboratory: “The opportunity to study the human brain is an extraordinary resource for the institute and for the study of all types of brain diseases, not just Alzheimer’s disease “Halushka explained.
The MUSC team found that the brains of patients who died from Alzheimer’s had 34 percent fewer pericytes than healthy brains in the hippocampus, a part of the brain associated with learning and memory. The remaining pericytes had much higher levels of Fli-1.
The team then showed that an animal model of Alzheimer’s also showed loss of pericytes in the hippocampus, increased Fli-1, and impaired memory. Blockade of Fli-1 improved the performance of mice in behavioral tests aimed at evaluating memory: “The most interesting finding is that the Fli-1 inhibitor actually improved the cognitive deficits in the animal model because, in the end, that’s the only thing that matters.“, Halushka continued.
The team of experts also revealed that Fli-1 blockade in mice helped prevent the loss of pericytes and preserve the integrity of the blood brain barrier, as well as reduce the accumulation of beta-amyloid: “We weren’t expecting such a profound effect in mice, but to our surprise, the inhibitor actually workedFan said.
The next step for the MUSC team is to develop an RNA capable of silencing Fli-1 and thereby reducing brain inflammation that leads to cell death in Alzheimer’s. The goal would not be to eliminate Fli-1, as it plays important roles in the body, but to keep it at healthy levels.
“The exciting thing is this could be a new way of thinking about Alzheimer’s treatment that has never been thought of before.“Concluded Halushka. “This research opens up a whole new area for potential targets, not just Fli-1 but the pericyte itself ”.
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