Protein folding lags in early Parkinson’s

MICHIGAN STATE (US) — According to a new study, the protein “clumping” that sets off Parkinson’s disease is the result of a slower folding rate.

A team of researchers led by Basir Ahmad, a postdoctoral researcher at Michigan State University, has demonstrated that slow-wriggling alpha-synuclein proteins are the cause of aggregation, or clumping together, which is the first step of Parkinson’s.

Proteins, which are chain molecules composed of amino acids, do most of the work in cells. While scientists understand how proteins are structured, they do not yet know how they are built—a process known as folding.


When errors happen in folding, proteins clump together, form plaques such as those found in Parkinson’s disease, Alzheimer’s, and Lou Gehrig’s disease, and cause cells to degenerate.

Using lasers to investigate the protein alpha-synuclein, the scientists correlated the speed at which the protein rearranges with its tendency to clump, as reported in the journal Proceedings of the National Academy of Science.

A slower speed places the protein in a “dangerous regime,” a pace that allows it to develop sticky patches, aggregate, and cause cellular damage, says Lisa Lapidus, associate professor of physics and astronomy and co-author of the paper.

“There are many, many steps that take place in aggregation, but we’ve identified the first step,” she says.

“Finding a method to fight the disease at its first stage, rather than somewhere further down the road, can hopefully increase the success rate in which the disease is treated.”

The identification of this critical first step already has the researchers pursuing new ways to attack the disease. Lapidus is currently testing a number of naturally occurring compounds, such as curcumin, ECGC, and resveratrol, which could push the rearranging protein out of the danger zone.

“We are now looking for molecules that can alter the protein when it first begins to ‘misfold,’ which could eventually lead to the development of a drug that could prevent aggregation before it happens,” she says.

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