Parkinson’s Disease May Not Start With the Brain


Parkinson’s disease, a condition in which nerve cells in the brain malfunction and die, might not even originate in the brain. According to new research, Parkinson’s could start in the gut.

A study led by Duke University scientists found that stomach tissue holds the same protein found in neurons within the brain. The protein known as α-synuclein, or Lewy bodies, works to dissolve fluids within a cell.

One of the first noticeable signs of Parkinson’s disease is hand tremors. Credit: highwaystarz/123RF Stock Photo

For those suffering from Parkinson’s disease, the Lewy bodies become misfolded in the brain, the study said. The proteins that are misfolded can stick together in the brain, causing clumps and damage to neurons.

The study found that enteroendocrine cells (EECs) in the lining of the small intestine gravitated towards nerve cells, even acting like them. Once the EECs were observed behaving like nerve cells, the researchers were able to link the Lewy bodies, said lead author Richard Liddle.

“It was only afterwards that we started putting these things together – these cells have a lot of nerve-like properties, [so] let’s see if they also contain alpha-synuclein. And if they do, maybe they could be the source of Parkinson’s disease,” Liddle told Live Science.

After finding that the Lewy bodies were expressed in the EECs within the gut, the researchers found the protein in both the small and large intestine. Changes in gut bacteria have been associated with Parkinson’s disease before, and the researchers suggested the EECs play a larger role.

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“Although it is not clear how gut microbes influence the nervous system, it is possible that this occurs through EECs,” the study said. “Microbial generation of short-chain fatty acids (SCFA) has been implicated in Parkinson’s disease progression, and it is conceivable that this occurs through EECs, including cholecystokinin and peptide YY cells, which have been shown to express SCFA receptors.”

The discovery of the protein in the EECs provides a previously unrecognized origin of where changes to the protein could happen. It’s those changes that could link the gut to the brain, the study said.

“Should changes in α-synuclein conformation develop, leading to assembly and spread of α-synuclein in a prion-like manner, it is possible that EECs, by virtue of their neuronal connection, play a critical role in transmitting PD pathology from the gut to the brain,” the study said.

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Environmental influences have also been suspected in Parkinson’s disease patients for half a century, the study said. Individuals exposed to pesticides and herbicides have been associated with an increased risk for Parkinson’s disease, which could explain the changes of the EECs, Liddle said.

“Maybe it’s bacteria, maybe a toxin that people ingest,” he said. “Maybe they affect the endocrine cell and that corrupts the alpha-synuclein protein, and that spreads from the cell to the vagus nerve to the brain.”

If more research can support the hypothesis that Parkinson’s disease originates in the gut, there could be new and better ways to detect the disease earlier. There could even be new ways to treat the disease, Liddle said.

“It’s possible that if it starts in the gut, then you could create treatments that prevent abnormal alpha-synuclein formation in these cells,” Liddle said. “It’s possible you could develop dietary ways of treating those cells because those cells are lining the intestine. At this point, it’s difficult to imagine, but we will see.”