THE ESSENTIAL
- A molecule involved in cholesterol transport represents a common risk factor for Alzheimer’s and diabetes
- The cholesterol displacement pattern could be replicated in the brain to remove the proteins involved in Alzheimer’s
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In recent years, 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 at removing glucose from the circulation. blood, which leads to high blood sugar levels 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 in the brain.
Scientists at the Arizona University of Health Sciences (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 damaging changes that contribute to both Alzheimer’s disease and type 2 diabetes.“said Gregory Thatcher, professor of pharmacology and toxicology at the University of Arizona College of Pharmacy and co-author of the study.
Published in the journal ACS Pharmacology and Translational Science, the study looked at the process of reverse cholesterol transport, a process in which specific molecules transport excess cholesterol to be evacuated by 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 objective of this work was to succeed in modifying the trajectory of this protein in the brain. “Moving cholesterol to where it’s needed in the body has positive effects on many physiological processes and can help remove misfolded proteins that build up in the brain.“, explains Pr 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 preventing unwanted effects on the liver. The use of these compounds made it possible in particular to improve glucose tolerance and insulin sensitivity, as well as reduce weight gain, note the authors of the work.
Future research aimed at improving the properties of 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 from it.
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