A new study sheds light on why sometimes clumping proteins leads to degenerative brain diseases kill some cells while leaving others unharmed.
Researchers at Catholic University Leuven in Belgium believe normally innocuous proteins, known as prions or amyloids, become dangerous when they can be engineered to clump into fibers similar to those formed by proteins involved in Alzheimer’s, Parkinson’s and brain-wasting prion diseases like Creutzfeldt-Jakob disease.
According to an article in Science News, the research shows that cells that normally rely on the protein’s normal function for survival die when the proteins clump together. But when the cells don’t need the protein, they remain unharmed by the grouping.
Clumpy proteins are twisted forms of normal proteins that have been identified in many nerve-cell-killing diseases. These proteins can often make other normal copies of the protein go rogue.
Biophysicists Frederic Rousseau and Joost Schymkowitz of Catholic University Leuven, engineered a protein for vascular endothelial growth factor receptor 2, or VEGFR2 to clump.
They clipped off a portion of the protein and caused it to cluster with other proteins, creating an artificial amyloid.
The scientists observed that masses of the protein fragmented and could aggregate with and block the normal activity of VEGFR2.
When the researchers added the protein fragments to human umbilical vein cell grown in a lab dish, the cells died because the receptor could no longer transmit hormone signals the cells need to survive.
However, biophysicist Priyanka Narayan of the Whitehead Institute for Biomedical Research in Cambridge, Mass, said that human embryonic kidney cells and human bone cancer cells remained healthy, which suggests that amyloid proteins aren’t generically toxic to cells.
Narayan said this likely means that rogue proteins target specific proteins and only kill cells that rely on those proteins for survival.
Scientists will continue to study why these groupings end up harming cells, as they also research which jobs many of these proteins normally perform.
Salvador Ventura, a biophysicist at the Autonomous University of Barcelona, said the new engineered proteins may be beneficial to inactivate specific proteins to fight cancer and other diseases.
The study, which appeared in Science on Nov. 11, can be viewed here.