Researchers at the Technion Identify the Mechanism Leading to the Accumulation of Proteins Involved in the Development of Alzheimer’s Disease
New Discoveries in the Development of Alzheimer’s Disease in a Study Led by Professor Michael Glickman and Dr. Inbal Maniv from the Faculty of Biology at the Technion Were Published in Nature Communications.
Alzheimer’s disease was named after the German researcher Dr. Alois Alzheimer, who first described it in 1906. The disease is characterized by the degeneration and death of nerve cells, processes that lead to a progressive impairment of cognitive abilities. It occurs typically in adults over the age of 65, but a small percentage of all Alzheimer’s patients are hereditary cases that affect younger patients.
Today, Alzheimer’s disease is commonly divided into two types – familial and sporadic. Familial Alzheimer’s disease is a rare disease that is caused by genetic mutations. By contrast, the underlying mechanism of the more prevalent Sporadic Alzheimer’s disease is unclear and was the focus of the research conducted by Dr. Maniv and Professor Glickman, Dean of the Faculty of Biology.
Toxic proteins accumulate in the brains of Alzheimer’s patients. The mechanism of accumulation in familial patients is clear because there is an obvious link between the known mutations and the proteins that accumulate. In sporadic Alzheimer’s disease, on the other hand, the trigger for protein accumulation is unknown.
As protein experts, the Technion researchers proposed that the accumulation of toxic proteins in the brain is due to a disruption in the protein clearance mechanism, also known as the ubiquitin-proteasome system. To test their hypothesis, they established a model system out of human neurons that allowed them to examine the involvement of the ubiquitin system in the development of the disease. The published article describes results whereby damage to the ubiquitin system leads to the accumulation of toxic proteins even in healthy tissue, mimicking the typical Alzheimer’s pathology.
To assess the importance of their findings, the researchers went on to engineer an RNA molecule that specifically silences one of the components of the ubiquitin system. Treatment with this molecule ameliorated the pathology in their experimental model. The team proposes that this RNA molecule will serve as a prototype for the development of effective treatments. The past few years have seen major advancements in the packaging and delivery of bio-active RNA molecules as therapies. With proper modifications and packaging, this interference RNA against the target that the team has identified should yield promising results in a clinical setting. This discovery highlights the importance of the ubiquitin system in clearing defective proteins to maintain healthy cells, while a disruption in this system may lead to the development of the disease.
The Technion researchers believe that beyond the findings presented in the article, the platform they developed may be used to screen drugs for the treatment or prevention of sporadic Alzheimer’s disease. They add that this platform will help reduce animal experiments in the development of new Alzheimer’s therapies.
Participating in the research were Mahasen Sarji, Anwar Bdraneh, Dr. Yaron Fuchs, and other researchers from the Technion, in collaboration with researchers from Tel Aviv University, Maastricht University in the Netherlands, and the University of Glasgow in Scotland. The research was supported by the Israel Science Foundation, the philanthropic Schmidt Futures, and the BIRAX – Alzheimer Society partnership.
For the article in Nature Communications
Read more about the study:
https://www.eurekalert.org/news-releases/1003532 [
https://www.jpost.com/health-and-wellness/article-761491 [
