Misfolded Proteins Travel in Huntington’s Disease

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The movement of proteins involved in neurodegenerative diseases could serve as a target for future therapies

Sep 16, 2014 | |

The first step to treating or preventing a disease is often finding out what drives it. In the case of neurodegenerative disorders, the discovery two decades ago of what drives them changed the field: all of them—including Alzheimer's, Parkinson's, Huntington's and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease)—involve in brain cells.

Typically when a protein misfolds, the cell destroys it, but as a person ages, this quality-control mechanism starts to fail and the rogue proteins build up. In Huntington's, for example, —used for many cell functions—misfolds and accumulates. Symptoms such as muscular difficulties, irritability, declining memory, poor impulse control and cognitive deterioration accompany the buildup.

Mounting evidence suggests that not only does the accumulation of misfolded proteins mark neurodegenerative disease but that from one cell to another causes the disease to progress. Researchers have seen misfolded proteins travel between cells in Alzheimer's and Parkinson's. A series of experiments reported in in August suggests the same is true in Huntington's. ( is part of Nature Publishing Group.)

In their tests, researchers in Switzerland showed that mutated huntingtin protein in diseased brain tissue could invade healthy brain tissue when the two were placed together. And when the team injected the mutated protein into a live mouse's brain, it spread through the neurons within a month—similar to the way prions spread, says Francesco Paolo Di Giorgio of the Novartis Institutes for BioMedical Research in Basel, who led the research. Prions are misfolded proteins that travel through the body and confer their disease-causing characteristics onto other proteins, as seen in mad cow disease. But it is not known if misfolded proteins involved in Huntington's convert other proteins as true prions do, according to Di Giorgio.

Scientists have yet to establish that the movement of bad proteins is critical for the progression of the disease, notes Albert La Spada, a geneticist at the University of California, San Diego, who was not involved in the study. But if it turns out that traveling is essential, then therapies may be able to target the pathway. “If we can find out how it's occurring,” La Spada says, “then we might be able to come up with treatments to prevent it.” And those treatments could potentially apply to the other neurodegenerative diseases.

The next step is crucial. Researchers will try to block the spread of misfolded protxeins and see if that improves symptoms or slows progression. Finding therapies for these diseases is paramount. Approximately alone are diagnosed every year in the U.S., and experts estimate the prevalence will at least double by 2030 because of an aging population.