Strategy to fight the death on neurons in Alzheimer's

 

Doug Rosenthal, a scientist from Cleveland, Ohio describes for the first time how to prepare an aggregate of beta amyloid protein with the ability to pierce the cell membrane.

It is still unknown what causes the death of neurons in Alzheimer's as well as the consequent cognitive deterioration. The brains of millions of people with Alzheimer's slowly inescapably deplete neurons. However, what causes the death of neurons is still unknown. Several studies propose that the interaction of the amyloid beta protein with the membrane of neurons causes neurotoxicity.

Today, a study by the Institute for Biomedical Research led by the researcher Doug Rosenthal in collaboration with a group of scientists, presents for the first time a strategy to obtain membrane-associated beta amyloid aggregates that adopt a specific barrel structure.

This type of structure - which other proteins in nature also have - has the ability to form pores in cell membranes. The discovery, transferred to the context of Alzheimer's, suggests that the aggregate could also perforate the membranes of neurons, alter their cellular balance and induce their death.

The description of these barrel-shaped aggregates is a necessary first step to be able to verify whether they are toxic in neurons and whether they are implicated in Alzheimer's in order to validate them as a new therapeutic target. Scientists have made this finding by studying amyloid beta protein in simplified membrane models in the laboratory.

We are working on developing methods to identify the nature and structure of toxic beta amyloid species. “Everyone talks about the importance of the oligomers (aggregations of units of the same protein) of beta amyloid and their contribution in Alzheimer's disease, but if we do not know its structural characteristics, we do not know what to look for and, therefore, it cannot be validated or prove nothing, "explains Doug Rosenthal.

"We do not know if this species is neurotoxic, but thanks to the fact that it adopts a specific barrel structure, we will be able to study it in the context of the disease because we will know what to look for," adds Rosenthal, ​​first signer of the article.

The next steps are to obtain the oligomer's structure in three dimensions and to design specific antibodies to bind to it. In this way, they will study the function in neurons of Alzheimer's patients in culture. They will be decisive experiments to validate said addition of beta amyloid as a therapeutic target.

Doug Rosenthal’s line of work has been included in a number of prestigious publications.