American scientists have identified a small molecule that could help regulate cholesterol levels in the brain. The researchers put forward the hypothesis of a new therapeutic target in the management of Alzheimer’s disease.
- A molecule involved in cholesterol transport represents a common risk factor for Alzheimer’s and diabetes
- Cholesterol-moving pattern could be replicated in the brain to eliminate proteins involved in Alzheimer’s
In recent years, the scientific literature has tended to establish similarities between the mechanisms involved in Alzheimer’s disease and type 2 diabetes. Type 2 diabetes occurs when insulin becomes less effective in removing glucose from the circulation blood, which leads to high blood sugar and can cause abnormal cholesterol levels. A similar situation occurs in Alzheimer’s disease, except that instead of affecting the body as a whole, the effects are localized to the brain.
Scientists from the University of Health Sciences in Arizona (USA) have studied this link closely. “Alzheimer’s disease and diabetes have many common causes. Our goal was to develop a way to identify compounds that could counteract the many detrimental changes that contribute to both Alzheimer’s disease and type 2 diabetes.“, explains Gregory Thatcher, professor of pharmacology and toxicology at the University of Arizona College of Pharmacy and co-author of the study.
Published in the magazine ACS Pharmacology and Translational Science, the study focused on the process of reverse cholesterol transport, a process during which specific molecules transport excess cholesterol to evacuate it through the liver. More specifically, the scientists studied the action of apolipoprotein E (APOE), one of the proteins involved in the reverse transport of cholesterol, which also represents a genetic risk factor in Alzheimer’s disease and diabetes. type 2.
Better insulin resistance and reduced weight gain
The aim of this work was to succeed in modifying the trajectory of this protein in the brain. “Moving cholesterol to where it is needed in the body has positive effects on many physiological processes and can help eliminate misfolded proteins that accumulate in the brain“, explains Prof. Gregory RJ Thatcher, who participated in the study.
The team of scientists tested the effects of small molecules (CL2-57) that could improve the function of another cholesterol transporter called ABCA1 in the body, while avoiding adverse effects on the liver. The use of these compounds notably improved glucose tolerance and insulin sensitivity, as well as reduced weight gain, note the authors of the work.
Future research aimed at improving the properties of the CL257 molecules is planned, in order to increase their levels in the brain and to develop a treatment. The long-term goal will then be to determine which patients with Alzheimer’s disease (or another form of dementia) will benefit.
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