Scientists at Massachusetts General Hospital have discovered the mechanism of formation of the beta-amyloid protein, which plays a key role in the development of Alzheimer's disease. The study is published in the prestigious journal Cell Reports .
Beta-amyloid, the excessive accumulation of which damages neurons and provokes dementia, is formed in the axons of nerve cells - long processes through which impulses are transmitted. Previously, it was known that the protein arises as a result of the process of palmitation, when a fatty acid residue is added to its precursor APP. Now it has become clear that special areas of the cell membrane - the so-called mitochondria-associated ER membranes (MAM) - are actively involved in this.
MAMs transport the precursor protein palAPP in the form of membrane vesicles inside the axon. They deliver it to the cell surface, where beta-amyloid is formed. The uniqueness of the discovery is that this process occurs precisely in axons, and therefore they are the main "arena" of brain damage in Alzheimer's.
In experiments with three-dimensional cultures of nerve cells, the scientists were able to confirm the role of MAM. Moreover, using a drug that blocks the sigma-1 receptor (S1R) — a key element in the assembly of MAM — the researchers were able to significantly reduce the production of beta-amyloid.
This finding opens up new possibilities for treatment. S1R could be a convenient target for therapies that could slow or even stop the early stages of Alzheimer's disease. Scientists believe that this discovery could pave the way for the development of effective drugs against one of the most common types of dementia in the world.
