Parkinson’s: Dietary compound moves toxic protein from gut to brain
A recent study deepens our understanding of how Parkinson’s disease begins in the gut.
Parkinson’s disease is a neurodegenerative condition.
Brain cells in the substantia nigra — a region vital for motor control — slowly break down.
The most common Parkinson’s symptoms are rigidity and tremor.
Other symptoms include some other physical changes and some psychological issues.
The condition is most common in older adults. Therefore, as the population grows older, Parkinson’s is likely to become an even greater problem.
To date, however, there is no cure and no way to prevent the disease from progressing.
A protein called alpha-synuclein plays a pivotal role in Parkinson’s; it clumps together to form part of larger structures called Lewy bodies. These appear to kill brain cells.
Paraquat and Parkinson’s risk
Scientists still do not know exactly why Parkinson’s disease occurs in some people but not others, but they are confident that both genes and the environment are involved.
A potential risk factor that has sparked debate is exposure to a herbicide called paraquat. Once widely used, the United States banned it in 2007.
Experiments have demonstrated that administering paraquat can cause Parkinson’s-like symptoms, or Parkinsonism, in rodents. However, the levels of pesticide the scientists used in those experiments are way above what a human would ever experience in reality.
Recently, researchers at Penn State College of Medicine in Hershey wanted to find out whether or not contact with paraquat — at realistic levels of exposure — could, indeed, increase the risk of developing Parkinson’s disease.
The scientists wanted to understand exactly how this chemical could travel from the stomach to impact protein buildup in the brain. They have now published their results in the journal NPJ Parkinson’s Disease.
Specifically, the scientists were interested in testing the theory that paraquat, once in the stomach, causes alpha-synuclein to be misfolded and then helps it travel to the brain.
Scientists believe that alpha-synuclein runs along the vagus nerve, which itself runs between the stomach and the brain. In fact, recent studies have shown that the vagus nerve has a direct connection with the substantia nigra, making it a prime suspect in Parkinson’s disease.
This direct link also helps explain why digestive problems often precede the motor symptoms of Parkinson’s by several years.
To investigate, the researchers fed rats small doses of paraquat for 7 days. They also fed them lectins, which are sugar-binding proteins present in foods such as raw vegetables, eggs, and grains.
Manufacturers of some types of medication also use lectins; they act as chaperones, helping deliver drugs to the brain or stomach. In the past, scientists have shown an association between taking drugs that contain lectin and developing Parkinsonism. However, they have not yet proven a causal link.
The investigators believe that lectins might form the link between paraquat and Parkinson’s.
After the 7-day trial, the team waited a further 14 days before testing the animals. The scientists then assessed motor function and looked for other markers of Parkinson’s. As expected, they identified Parkinson’s-related changes.
To check their findings, the researchers explored further.
“We administered levodopa, which is a common medication for Parkinson’s disease. We saw a return to almost normal types of motor responses, which was a clear indication that we were looking at some sort of Parkinsonism.”
Senior study author Prof. Alberto Travagli
The role of the vagus nerve
In another arm of the study, the team disconnected the vagus nerve from the stomach of some rats before beginning the 7-day intervention.
These animals did not develop Parkinsonism, demonstrating that the vagus nerve is the probable route the misfolded alpha-synuclein takes.
As study co-author Prof. Thyagarajan Subramanian explains:
“We were able to demonstrate that if you have oral paraquat exposure, even at very low levels, and you also consume lectins […] then it could potentially trigger the formation of this protein — alpha-synuclein — in the gut. Once it’s formed, it can travel up the vagus nerve and to the part of the brain that triggers the onset of Parkinson’s disease.”
This series of experiments demonstrates how the interplay between two ingested compounds can conspire to create and then transport toxic protein structures from the gut to the brain.
In the future, the researchers plan to explore whether or not certain dietary modifications or drugs might be able to interfere with either the production of alpha-synuclein or the protein’s journey from the gut to the brain.