Israeli Scientists Make Breakthrough in Understanding the Onset of Sporadic Alzheimer’s Disease

Professor Michael Glickman, Mahasen Sarji,Dr. Inbal Maniv and Anwar Bdraneh.(Technion spokesperson’s office

Researchers at Israel’s Technion in Haifa made a major breakthrough in understanding the onset of sporadic Alzheimer’s Disease; they uncovered the mechanism that causes the accumulation of proteins involved in the disease’s development. Sporadic Alzheimer’s Disease is the most common form, occurring in people with no family members who have suffered from it as well.

The study of Alzheimer’s Disease was led by Professor Michael Glickman and Dr. Inbal Maniv from the Faculty of Biology at the Technion and their results 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.

Alzheimer’s disease is a progressive neurodegenerative disorder that gradually destroys memory and thinking skills, and eventually, the ability to carry out the simplest tasks. It is the most common cause of dementia in people over the age of 65.

Alzheimer’s disease is caused by the abnormal build-up of proteins in and around brain cells. These proteins form plaques and tangles that disrupt the communication between neurons and eventually lead to cell death.

There is no cure for Alzheimer’s disease, but there are treatments that can help to manage the symptoms and slow the progression of the disease. These treatments include medications, lifestyle changes, and cognitive therapy.

Today, Alzheimer’s disease is commonly divided into two types – familial and sporadic. Familial Alzheimer’s disease is a rare condition, 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 study conducted by Dr. Maniv and Professor Glickman.

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, Prof. Glickman’s research group 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, the group established a model system of human neurons that allowed them to examine the involvement of the ubiquitin system in the development of the disease. In the published article, they describe their results: damage to the ubiquitin system leads to the accumulation of toxic proteins even in healthy tissue, mimicking the typical Alzheimer’s pathology.

The researchers’ discovery is important because it highlights the importance of the ubiquitin system in clearing defective proteins to maintain cell health. Disruption in this system can lead to the development of disease. Additionally, the researchers’ engineering of an RNA molecule that specifically silences one of the components of the ubiquitin system and ameliorates the pathology in their experimental model suggests that this RNA molecule could 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, the interference RNA targeting the component that the team has identified could yield promising results in a clinical setting.

This discovery highlights the potential of RNA interference (RNAi) as a therapeutic approach for a variety of diseases. RNAi is a natural process that uses small RNA molecules to silence gene expression. By targeting specific genes, RNAi can be used to modulate the production of proteins that are involved in disease development.

RNAi therapies have several advantages over traditional small molecule drugs. They are highly specific and can be used to target genes that are difficult to drug with traditional methods. Additionally, RNAi therapies are generally well-tolerated and have few side effects.

However, there are also some challenges that need to be addressed before RNAi therapies can be widely used in the clinic. One challenge is the development of effective delivery systems for RNAi molecules. RNAi molecules are large and fragile, and they need to be delivered to the target cells in a way that protects them from degradation. Another challenge is the potential for off-target effects, where RNAi molecules silence genes that are not intended to be silenced.