Alzheimer's disease: where will we cut?

The accuracy of the impact of a new drug for the treatment of Alzheimer's disease will try to increase

Anna Kerman, XX2 century, based on the materials of Medicalexpress: Steering an enzyme's 'scissors' shows potential for stopping Alzheimer's disease

A new study has demonstrated that by changing the point of application of the action of a new drug, it is possible – at least theoretically – to influence Alzheimer's disease.

Previously, scientists have already discovered two critical stages in the formation of beta-amyloid protein, which forms amyloid plaques in patients with Alzheimer's disease. Now researchers are studying possible ways to destroy the biochemical process of converting the precursor protein beta-amyloid into the final toxic form.

The last drug tested was the enzyme BACE1 (beta-secretase 1), which "cut" the precursor protein. However, as it turned out, the use of the drug is accompanied by serious undesirable effects. In particular, BACE1 disrupts the synthesis of myelin, a protein that protects nerve cells.

Professor of psychiatry at the University of British Columbia (University of British Columbia) and researcher of Alzheimer's disease Weihong Song (Weihong Song) found that by changing the location of the "cut" of the protein, it can help in achieving a therapeutic goal and at the same time reduce the number of undesirable consequences. Song's work was based on the discovery of two rare mutations: the first was found in Italians suffering from an early form of Alzheimer's disease, the second – in residents of Iceland, in whom the onset of the disease was delayed. The researchers became interested in the diametrically opposite effect of mutations, since they both affected the same point in the molecular chain of the precursor protein, changing 1 of its 770 amino acids to another.

As reported in an article published in the Journal of Neuroscience (BACE1 Cleavage Site Selection Critical for Amyloidogenesis and Alzheimer's Pathogenesis), scientists led by Professor Song injected one group of mice with a virus containing an "Italian" mutation, while other animals received an "Icelandic" version of the virus. Further investigation showed that the amino acid substitution affected where the precursor protein was "cut". The "Icelandic" mutation led to the formation of a shortened beta-amyloid molecule. Such an amyloid did not become "sticky" and was not capable of plaque formation. On the contrary, the "Italian" mutation contributed to the synthesis of an elongated version of beta-amyloid, which is more "sticky" and easily turns into a plaque.

The scheme of the molecular "scissors" BACE1
depending on the presence of a particular mutation.

It turned out that all this is a matter of place. One mutation led to the appearance of breaks at one point of the molecular chain, and the other at another. But the final decrease in the level of toxic protein can turn into years of productive life until the onset of cognitive impairment.

"If we manage to change the place of application of the "scissors" BACE1, the point where the drug "cuts" the precursor protein, we will get a highly accurate way to slow down the formation of plaques that does not affect other processes," explains Professor Song. - This gives us a new goal in the search for a cure – instead of a club, we want to give doctors something more like a scalpel."

Portal "Eternal youth" http://vechnayamolodost.ru  20.07.2017