18 April 2019

Alpha Sheets vs Beta Amyloid

Alzheimer's disease is an incurable disease in which toxic clots of beta–amyloid protein accumulate in brain cells. Recently, scientists have managed to construct a synthetic peptide that can prevent the accumulation of beta-amyloid at the earliest stages. This peptide consists of 23 amino acids and has an alpha-leaf structure. The sheets bind to newly formed beta-amyloid clots and stop their accumulation.

Forms of beta-amyloid

The formation of a toxic form of beta-amyloid is a hallmark of Alzheimer's disease, but not all forms of beta-amyloid are toxic. Beta-amyloid monomers perform important work in brain cells.

However, in people with Alzheimer's disease, individual beta-amyloid molecules are grouped into oligomers, which can contain up to 12 monomers. With such a complex structure, the protein does not form the structure necessary to perform its functions. Oligomers continue to grow, and eventually form plaques.

At first, there was an opinion that plaques are the most toxic form of beta–amyloid, which causes symptoms of Alzheimer's disease, such as memory loss and the ability to think. However, due to the growing amount of evidence, an increasing number of experts suggest that the early stages of the formation of the beta-amyloid oligomer are much more toxic to brain cells.

Synthetic peptide attacks beta-amyloid

Alpha-peptide sheets were created in order to block the formation of beta-amyloid at the stage of oligomer formation.

In the future, it will be possible to develop synthetic peptide alpha sheets, the structures of which will "complement" the accumulations of beta-amyloid, leaving biologically active monomers intact.

The prototype for the production of three-dimensional molecules of various shapes was protein synthesis in cells. The first step in creating a polypeptide is folding a long chain into one of several basic structures.

Professor Daggett's team discovered in a previous paper in which they modeled protein synthesis on computers, one such basic structure – the alpha sheet. A recent study has shown that beta-amyloid oligomers take the form of an alpha leaf as they form longer clumps and plaques.

It also shows that the synthetic alpha-peptide sheet binds only to beta-amyloid alpha-oligomer sheets and neutralizes their toxicity.

The Big drop in beta-amyloid oligomers

Scientists used traditional spectroscopy techniques to observe how beta-amyloid progresses from monomers to oligomers to plaques in cultured human brain cells.

It was shown that the treatment of mouse brain tissue samples with alpha-sheets of synthetic peptide led to a decrease in the toxicity of beta-amyloid oligomers by 82%, and in the brains of living mice, the level of formation of beta-amyloid oligomers decreased by 40% during the day.

Experiments on Caenorhabditis elegans worms have shown that treatment with a synthetic peptide can delay paralysis caused by beta-amyloid plaques. The experiment also showed less intestinal damage, which develops when worms feed on bacteria that produce beta-amyloid.

The study also showed that it is possible to use alpha sheets of synthetic peptide to check the levels of beta-amyloid oligomers.

Professor Daggett and her team are already experimenting with new versions of synthetic proteins to find those that can neutralize beta-amyloid oligomers more effectively.

Elena Panasyuk, portal "Eternal youth" http://vechnayamolodost.ru / based on Medical News Today: Alzheimer's: Synthetic protein blocks toxic beta-amyloid.


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