The hallmark of Parkinson’s disease is the formation of aggregates of the protein alpha-synuclein, which are toxic to neurons and promote the loss of brain function. A new animal study suggests these aggregates can form in the gut and, in the course of months, spread to the brain.
These findings were recently discussed at the Society for Neuroscience 2016, in San Diego, in the presentation, “Progression Of Parkinson’s-Like Pathology Following Inoculation Of Alpha-Synuclein Preformed Fibrils In The Gut,” by Collin Challis from Caltech.
Previous studies have suggested that the gut could be involved in Parkinson’s disease. Researchers have found alpha-synuclein aggregates in the gut nerves during autopsies of both patients and individuals with aggregates in the brain but no symptoms. Parkinson’s patients also often report experiencing gastrointestinal problems, such as constipation, about 10 years before the start of movement anomalies, the most typical symptoms of the disease.
This evidence supports the idea that Parkinson’s disease may start in the gut, possibly due to bacteria or toxins.
Challis and his colleagues injected aggregates of alpha-synuclein into the stomach and intestine of mice. The team observed that the aggregates promoted the formation of new aggregates, and that these spread to the base of the brain three weeks later. Two months later, the aggregates had reached deep brain areas responsible for movement control and dopamine production — the neurons that die in people with Parkinson’s. Indeed, the injected mice showed reduced agility, similar to what happens in patients.
It is not yet clear what may trigger the formation of the aggregates in the gut, but previous studies suggest that this may be due to the presence of specific bacteria in Parkinson’s patients. Indeed, some doctors have been trying to see whether antibiotics or fecal transplants may help in preventing the development of Parkinson’s.
“It could be that having the wrong bacteria in your gut triggers inflammation,” Sébastien Paillusson from King’s College London, said in a news release. “We know that inflammation makes synuclein more likely to aggregate.”
Another triggering factor for alpha-synuclein aggregation in the gut may be the exposure to certain chemicals, as some studies have shown that farmers exposed to certain pesticides and people who drink water from possibly contaminated wells are at higher risk of developing Parkinson’s disease. It may be that these chemicals induce damage to the gut and aggregation of alpha-synuclein.
“There are a lot of theories out there,” said Challis, in another news release. “Bacteria may produce compounds called curli that prompt alpha-synuclein to aggregate, a recent study suggests. Pesticides, acid reflux and inflammation are other possible culprits that could somehow increase alpha-synuclein clumps in the gut.”
Although questions remain to be answered, knowing that the gut may be the starting point for the development of Parkinson’s opens the possibility of stopping the disease before the most profound symptoms appear.