Scientists, including Veronica Ryan, a Brown neuroscience doctoral student, report in a new study that by imitating a natural process of cells, they prevented the formation of protein clumps associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
In lab cultures of human and yeast cells, the scientists stopped the harmful clumping of FUS proteins by exposing them to phosphorylation, a process that makes precise changes to the amino acid building blocks of proteins, increasing their negative electric charge. The research shows that the increase in charge causes the proteins to repel when they normally might aggregate.
The findings could eventually have positive implications for the treatment of ALS — commonly called Lou Gehrig’s disease — and dementia.
“No one has shown that you can use charge, and phosphorylation as a way to get charge, to disrupt these ALS-associated protein aggregates,” said co-corresponding author Nicolas Fawzi, an assistant professor in the Department of Molecular Pharmacology, Physiology and Biotechnology at Brown University.
Phosphorylation occurs in cells throughout the body for various reasons. Cells perform it on FUS proteins as part of a sequence of events related to DNA damage. In the new study, the researchers examined both natural phosphorylation and artificial phosphorylation by replacing specific amino acids in FUS proteins.
The study, conducted by a team of researchers at Brown, the Uniformed Services University, Johns Hopkins University, Lehigh University and the National Institutes of Health, appears in the EMBO Journal.
Read more of David Orenstein's article on protein clumps associated with ALS.