Scientists of the Massachusetts Hospital of the General Profile uncovered how the beta-amyloid protein, which plays a key role in the development of Alzheimer’s disease. Until now, the exact causes of this incurable and fatal form of dementia, which has been widespread throughout the world, remained for the secret researchers. In a new scientific work, the results of which were published in the Cell Reports magazine, it was shown that beta-amyloid is formed in axons of neurons and other cellular structures involved in the transmission of nerve impulses.
In previous studies, it is shown that beta-amyloid is formed when the residue of higher fatty acid is connected to its predecessor (AMYLOID Precursor Protein, App) – this process is called palmitizing. 40 percent of beta-amyloid is produced inside axons, long irregularity processes for which the pulse is transmitted through the synaps to short processes (dendrites) of adjacent cells.
To transport important proteins outside, the cell uses rafts – special areas of the membrane (in this case of the endoplasmic reticulum), inside which monitor many cellular functions. RAFTs include ER-membrane associated with mitochondria (Mam) – Plots of reticulum, which are associated with cellular energy by mitochondria. Mam is capable of moving inside the axon in the form of membrane bubbles, and mitochondria in their composition support the functioning of synapses.
In the course of the study, scientists used three-dimensional cultures of nerve cells that serve as a primitive model of the brain, affected by Alzheimer’s disease. They conducted a biochemical analysis to identify the predecessor of beta-amyloid and its palmized form (Palapp), and also studied the behavior of Mam inside axons. It turned out that it was MAM that helps the delivery of Palapp to the cell surface, where the protein is released as a beta-amyloid. This feature of mothers performs exclusively in axons, where beta-amyloid causes most of the damage.
With a medicinal product that blocks the SIGMA-1 receptor (S1R), participating in the assembly of the MAM, the scientist managed to drastically reduce the production of pathogenic protein. Thus, S1R can serve as a comfortable target for therapy, slowing down or stopping the early stage of Alzheimer’s disease, on which experts believe, treatment can still be effective.