misfolded synuclein leads to parkinson’s spread

Image of a stained Lewy body

Research from my alma mater, The University of Pennsylvania, reveals some details on how Parkinson’s disease spreads throughout neural cells. The research led by Virginia Lee in the Department of Pathology and Laboratory Medicine has found that the protein α-synuclein plays a key role. When it is misfolded it passes through neural cells and causes cellular death and the formation of Lewy bodies. From Scientific American:

Parkinson’s disease has two distinct features: clumps of protein called Lewy bodies and a dramatic loss of nerve cells that produce the chemical messenger dopamine. When Lee’s team injected the misfolded α-synuclein into a part of the mouse brain rich in dopamine-producing cells, Lewy bodies began to form. This was followed by the death of dopamine neurons. Nerve cells that linked to those near the injection site also developed Lewy bodies, a sign that cell-to-cell transmission was taking place, say the researchers.

Greenamyre says that that is possible, but hasn’t yet been proved. “All of the cells affected in this paper were those directly in contact with the injection site,” he says.

Nevertheless, within six months of the injection, coordination of movement, grip strength and balance had all deteriorated in the mice, echoing what happens in people with Parkinson’s disease.

“It’s really pretty extraordinary,” says Eliezer Masliah, a neuroscientist at the University of California, San Diego. “We have been trying that experiment for a long time in the lab and we have not seen such dramatic effects.” The study lends theoretical support to the handful of biotechnology companies that are sponsoring clinical trials of α-synuclein antibodies for Parksinson’s, Masliah says. It should also spur research on how the protein gets in and out of cells, he adds.

Check out the details of the research in Science.