Researchers have uncovered a major reason why proteins that are the hallmark of Parkinson’s disease are toxic to neurons in the brain. The discovery could be key to finding a way to slow or halt the disease.
“It’s really exciting that we have found a mechanism we can target to create new treatments for this devastating disease.”
“It’s really exciting that we have found a mechanism we can target to create new treatments for this devastating disease,” says lead investigator J. Timothy Greenamyre, a neurology professor at the University of Pittsburgh School of Medicine.
Degenerating neurons contain large clumps of a protein called alpha-synuclein. People whose cells make too much alpha-synuclein or make a mutated form of the protein are at high risk of developing Parkinson’s because of the protein’s toxicity, Greenamyre and colleagues found.
They also demonstrated that the accumulation of alpha-synuclein is toxic because it disrupts the normal functioning of mitochondria—the tiny powerhouses responsible for generating a cell’s energy.
This results in the production of less energy and more damaging cellular waste, ultimately leading to neurodegeneration.
The researchers confirmed their findings in brain tissue from people with Parkinson’s. The results are detailed in a paper published in Science Translational Medicine.
“The effects of alpha-synuclein on mitochondria are like making a perfectly good coal-fueled power plant extremely inefficient, so it not only fails to make enough electricity, but also creates too much toxic pollution,” says Greenamyre.
Using cell cultures, the research team also found two ways to prevent the toxicity caused by alpha-synuclein: gene therapy that forced the neurons to make more of a mitochondrial protein called TOM20 protected them from the alpha-synuclein; and a protein that was able to prevent alpha-synuclein from sticking to TOM20 prevented alpha-synuclein’s harmful effects on mitochondria.
While more research is needed to determine whether these approaches could help people with Parkinson’s, Greenamyre is optimistic that one or both may ultimately make it into human clinical trials.
The DSF Charitable Foundation, the Ri.MED Foundation, the Consolidated Anti-Aging Foundation, the National Institutes of Health, the US Department of Veterans’ Affairs, the Blechman Foundation, the American Parkinson Disease Association, and the Government of India’s Department of Biotechnology supported the research.
Source: University of Pittsburgh