Toxic proteins accumulate in the brains of Alzheimer's patients. In the familial Alzheimer's patients, the accumulation mechanism is clear since there is a circumstantial relationship between the mutations and the identity of the defective proteins. In the random disease, on the other hand, the reason for the accumulation of the defective proteins was unknown
New discoveries in the development of Alzheimer's disease in research led by Prof. Michael Glickman and Dr. Inbal Maniv from the Faculty of Biology at the Technion published in Nature Communications.
Alzheimer's disease got its name from the German researcher 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 gradual impairment of the individual's cognitive abilities. It is typical for adults over the age of 65, but there are not many cases that are inherited and affect younger patients. Today it is customary to divide Alzheimer's disease into two types - familial and random (sporadic). Familial Alzheimer's disease is a rare disease (a few percent of all Alzheimer's patients) resulting from hereditary genetic mutations. Random Alzheimer's disease, which as mentioned is more common, is less clear in terms of the mechanism, and is the one that was at the heart of Dr. Maniv and Prof. Glickman's research.
Toxic proteins accumulate in the brains of Alzheimer's patients. In the familial Alzheimer's patients, the accumulation mechanism is clear since there is a circumstantial relationship between the mutations and the identity of the defective proteins. In the random disease, on the other hand, the cause of the accumulation of the defective proteins is unknown. As experts in protein research, the Technion researchers suggested that the accumulation of toxic proteins in the brain results from a disruption in the protein clearance system - also known as the ubiquitin system. They developed a model system from human nerve cells, which makes it possible to examine the involvement of the ubiquitin system in the development of the disease. The article describes findings from this system, which indicate that damage to the ubiquitin system in healthy nerve cells causes the accumulation of toxic proteins in a way that simulates the pathology typical of the disease in the brain.
The researchers were not satisfied with deciphering the cause of the accumulation, but also tested their thesis by repairing the damage using an RNA molecule that they engineered in favor of Deliberate silence of one of the components of the ubiquitin system. To their delight, the treatment using this molecule improved the condition of the nerve cells in the system. The research team suggests that this RNA molecule will serve as a prototype for the development of effective treatments to prevent Alzheimer's symptoms and possibly even treat patients.
In recent years there has been significant progress in the packaging of RNA molecules and their delivery to patients. The researchers hope and estimate that with minor changes in composition and appropriate packaging, this RNA molecule will be able to produce promising results in a clinical setting. The discoveries of the Technion researchers clarify the importance of the ubiquitin system in preventing Alzheimer's and the connection between disruption of this system and the development of the disease.
The Technion researchers estimate that beyond the findings presented in the article, the platform they developed may be used to scan drugs for the treatment or prevention of random Alzheimer's. They add that this platform will help reduce animal experiments in the development of new treatments for the disease.
Mahasen Serji, Anwar Badrana and Dr. Yaron Fox and other researchers from the Technion participated in the study in collaboration with researchers from Tel Aviv University, Maastricht University in the Netherlands and Glasgow University in Scotland. The research was funded by the National Science Foundation, the philanthropic foundation Schmidt Futures, and the BIRAX partnership and the Alzheimer Society.
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