Scientists have revealed the secret of the occurrence of a fatal brain disease

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Massachusetts Hospital scientists revealed how the protein beta- amyloid, which plays a key role in the development of Alzheimer's disease, or “senile dementia”. Until now, the exact causes of this form of dementia remained a mystery to researchers.

It turned out that beta-amyloid is formed in the axons of neurons and other cellular structures involved in the transmission of nerve impulses.

In the previous studies have shown that beta-amyloid is formed when a residue of a higher fatty acid is attached to its precursor (amyloid precursor protein, APP) – this process is called palmitication.

40% of beta-amyloid is produced inside axons, the long processes of nerve cells, after which the impulse is transmitted through the synapse to the short processes (dendrites) of neighboring cells.

To transport important proteins outside, the cell uses rafts – special areas membranes (in this case EPR), within which many cellular functions are controlled.

Rafts include mitochondria-associated ER-membranes (MAM) – areas of the reticulum that are connected to mitochondria, which supply the cell with energy. MAMs are able to move inside the axon in the form of membrane bubbles, and the mitochondria in their composition support the functioning of synapses.

During 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 performed a biochemical analysis to detect the precursor of beta-amyloid and its palmitized form (palAPP), and also studied the behavior of MAM inside axons.

It turned out that it is MAM that helps deliver palAPP to the cell surface, where the protein is released in the form of beta-amyloid. MAM performs this function purely in axons, where beta-amyloid causes most of the damage.

With the help of a drug that blocks the sigma-1 receptor (S1R), which is involved in the assembly of MAM, scientists managed to dramatically reduce production of a pathogenic protein.

So, S1R may serve as a convenient target for therapy that slows or stops the early stage of Alzheimer's disease.