By james art Irvine, California, October 24, 2024 — A research team led by scientists at the University of California, Irvine is one step closer to unraveling the mysterious origins of Parkinson’s disease, discovering that the incurable disorder appears to take root in the human gut.
“Parkinson’s disease occurs when proteins accumulate in regions of the brain that control body functions,” said Elizabeth Bess, a professor in the Department of Chemistry and lead researcher behind the work. “When these proteins build up in that part of the brain, it causes the neurons to die, and then people can’t move their body the way they’d like.”
Parkinson’s disease causes patients to lose voluntary control over their body movements. It affects about a million people in the US
Bess’ lab specializes in the study of the human microbiome—the community of trillions of microbes that live in your gut and are not genetically related to you. What Bess’ interdisciplinary team discovered is that the protein chunks that build up in the brain and lead to Parkinson’s appear to form in the gut as a result of the well-known E. coli bacteria that live in our intestines.
The team found that the waste produced by E. coli causes the formation of protein fragments – called alpha-synuclein aggregates. The team published their work in ACS Chemical Neurologyand in ACS Chemical Biology.
“There is evidence that these disease-causing protein clumps can travel from the gut to the brain along the vagus nerve, which connects these organs,” Bess said. “So if you can stop the aggregates from forming in the gut, there’s a chance the proteins won’t reach the brain and cause Parkinson’s disease.” And now that we know how these protein aggregates form, we can find ways to prevent them from forming.
Bess’ team, working with Penn State electrical engineering professor Aida Ebrahimi, recently found that a component of coffee can prevent protein aggregates from forming in intestinal cells. “Other studies have shown that drinking coffee reduces the risk of developing Parkinson’s disease, and our findings shed light on how this might work,” said Bess, whose team’s findings lay the groundwork for new treatments that target the proteins before they ever succeeded. to the brain.
Now that the intestinal origin of the protein fragments is becoming clear, Bess and her team plan to reveal the journey of the protein fragments in greater detail. In collaboration with UC Irvine chemistry professor Jennifer Presser, Bess’ team tagged the proteins with bioluminescent molecules that emit light and are traceable as they move through the body.
“We can track the protein from the gut cells and see if it goes to the neurons, which is the proposed mechanism for getting from the gut to the brain,” Bess said. “Clumps of alpha-synuclein are found in the gut many years before disease symptoms appear, so there is a real window of opportunity to stop the formation of these pathogenic proteins before they become a bigger problem.”
The idea that treatment for a disease like Parkinson’s disease, which affects the brain, could start in the gut is new.
“The idea that Parkinson’s disease can start in the gut is a little strange in terms of the typical dogma of thinking about Parkinson’s disease,” Bess said. “But our research paints a map of how this is possible. We hope that our work will open new avenues for better treatments to help people with this disease.
Funding sources include the NIH National Institute of Neurological Disorders and Stroke and Scialog Grants jointly sponsored by the Research Corporation for Science Advancement, the Frederick Gardner Cottrell Foundation, and the Paul G. Allen Frontiers Group.
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