Have Proteins, Will Travel

New study shows that toxic proteins linked to C9orf72 can travel between neurons


One of the lingering mysteries in ALS research is understanding how the disease spreads from one motor neuron to another. In a new study in Cell Reports, a team of researchers led by Davide Trotti, a neuroscientist at the Jefferson Weinberg ALS Center, in the Vickie and Jack Farber Institute for Neuroscience at Thomas Jefferson University, and Piera Pasinelli, science director of the Packard Center, have identified one potential mechanism. They showed that small toxic proteins called dipeptide repeats (DPRs), produced as a byproduct of the C9orf72 repeat expansion, can travel between neurons and other brain cells called glia

Many neurodegenerative diseases, including ALS, Alzheimer’s, and Parkinson’s, are characterized by the buildup of misfolded proteins. Research in Alzheimer’s disease has shown that some of these misfolded proteins have the potential to spread from cell to cell throughout the nervous system in a process called seeding. The proteins spread from one nearby cell to another, although they can occasionally travel to cells that are further away. Although researchers have studied this process in Alzheimer’s disease, there has been much less work in ALS.

Scientists have long linked the misfolding of proteins like SOD1 and TDP43 to ALS, but the more recent discovery of the C9orf72 mutation, in which a sequence of six DNA bases is repeated hundreds or thousands of times, has identified a new type of toxic protein. The large number of repeats confuses the cellular machinery that turns DNA into protein. As a result, the cell accidentally transcribes the DNA sequence in the repeat, creating DPRs.

excerpt © 2016 The Robert Packard Center for ALS Research at Johns Hopkins. All rights reserved.