Journey of How Parkinson’s Begins in the Gut and Travels to the Brain

Onset of Parkinson’s disease is illuminated by researchers, who unveil a previously undiscovered process originating in the gut and progressing to the brain.

The team from Duke University in the US identified a protein found in the gut called alpha-synuclein that travels through the nervous system and reaches susceptible nerves in the brain. The new evidence that bolsters the gut-brain connection is reported in the journal JCI Insight (1^✔ ✔Trusted Source
Gut mucosal cells transfer α-synuclein to the vagus nerve

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“It’s when alpha-synuclein proteins become corrupted that this transport system becomes an issue,” said Rodger Liddle, Professor in the Department of Medicine at Duke University School of Medicine.

“If they are corrupted in the gut and are then able to spread to the brain, they could form clumps known as Lewy bodies, which are the hallmark of Parkinson’s disease and other forms of dementia,”

Mapping the Path of Parkinson’s Disease

Liddle added. Parkinson’s disease is a long-term degenerative disorder that impairs voluntary movement. It is estimated that up to 10 million people worldwide are living with the disease.
There is growing evidence that the gut plays a role in developing Parkinson’s. One clue is that gastrointestinal symptoms such as constipation often happen before motor skills decline.

Liddle and colleagues focused on specialized cells that line the gut called enteroendocrine cells. These cells react to their environment and sense toxicants like herbicides and pesticides in the intestine; they also harbor alpha-synuclein.

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In experiments with cell cultures and mice, the researchers found that enteroendocrine cells transport alpha-synuclein from gut mucosal cells to the brainstem via the vagus nerve — the body’s superhighway connecting the gut and brain.

“We hypothesize that something in the gut is corrupting alpha-synuclein, causing it to misfold,” Liddle said.

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“Whether this is toxicants or some other exposure, we don’t know. But we have demonstrated here that there is a route for pathologically misfolded alpha-synuclein to be transported from enteroendocrine cells to the brain, where they can aggregate to form Lewy body deposits.”

Liddle said the research team was able to stem the spread of alpha-synuclein by severing the vagus nerve in the animals. The finding sets the foundation for designing therapies that could block the transport system or reset the altered gut-brain signaling.

Reference:

1. Gut mucosal cells transfer α-synuclein to the vagus nerve
   – (https://insight.jci.org/articles/view/172192)

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