Chronic inflammation in the gut can drive body processes that lead to Parkinson’s disease, according to a study by scientists at the Van Andel and Roche Institute.
The study, published in Free neuropathology, is the last of a growing list linking the gut and the immune system to Parkinson’s. The researchers’ findings in an experimental mouse model of the intestinal inflammation track with several large-scale epidemiological studies showing an association between Parkinson’s and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease.
Epidemiological evidence from other groups indicates the risk of Parkinson’s in certain people inflammatory bowel disease it is treated with anti-TNF, a cure-all anti-inflammatory therapy, which suggests that reducing intestinal inflammation may have a promise in mitigating the onset of Parkinson’s.
“There is growing evidence that changes in the gut can affect a variety of neurological and psychiatric brain Patrik Brundin, MD, Ph.D., deputy scientific director of VAI and corresponding author of the study. “Parkinson’s is a complex disease with a wide range of factors that work together to cause its onset and progression. We need to better understand the likely influence of the gut on the development of Parkinson’s. This study provides new insights. and this new knowledge can facilitate the development of improved treatment approaches. “
In their disease models, the team found that chronic intestinal inflammation triggers a protein called alpha-synuclein to cluster in the walls of the colon, as well as in local immune cells called macrophages. A similar process can occur at both points in some people, such as those with inflammatory bowel disease, thus increasing the risk of developing Parkinson’s, as shown in studies from other groups.
Similarly, “sticky” alpha-synuclein aggregates also develop in the brains of people with Parkinson’s. For reasons that are not yet clear, these aggregates can clog the molecular machinery that keeps neurons alive. The resulting loss of some of these critical cells and the chemical messenger they produce, called dopamine, causes symptoms related to Parkinson’s movement, such as freezing and loss of voluntary movement. The additional development of alpha-synuclein aggregates throughout the brain may also be associated with the non-motor symptoms of the disease and may fuel its progression, which cannot be slowed or stopped with existing treatments.
The study also revealed this chronic inflammation in the gut early in life can exacerbate the concentration of alpha-synuclein throughout the brain in older mice. While it’s unclear how this happens, the team has two theories: first, they suggest that inflammatory chemicals can travel from the gut to the brain through the bloodstream, causing a runaway inflammatory immune response that leads to protein aggregation. Another idea is that alpha-synuclein aggregates can travel to the brain through the brain vague nerves, one of the body’s longest nerves and a “highway” between the gut and the brain. Once there, proteins can perform their toxic activity in the brain.
“We now know that whole-body systems contribute to Parkinson’s,” said Emmanuel Quansah, Ph.D., a postdoctoral fellow in Brundin’s lab and a key contributor and co-author of the study. “It was amazing to see protein aggregation pathology in the brain that reflected the pathology of the colon caused by inflammation. A particularly fascinating observation was the loss of dopamine-producing nerve cells, which play an important role in the onset. of Parkinson’s, in our models who had intestinal inflammation a year and a half earlier. “
It should be noted that the team also found that modulation of immune activation in the colitis mouse model by genetic or therapeutic means adjusted the level of alpha-synuclein groups in the colon upward or downward.
“Our results in mice, along with other people’s genetic and epidemiological data in humans, constitute a strong argument for further exploring systemic immune pathways for future therapies and biomarkers for Parkinson’s,” said Markus Britschgi, Ph.D. .D. Head of section of the Department of Research in Neurosciences and Rare Diseases of the Roche Innovation Center in Basel and corresponding author of the study.
Free neuropathology, DOI: 10.17879 / freeneuropathology-2021-3326
Van Andel Research Institute
Citation: Understanding bowel inflammation may contain clues to mitigate the onset of Parkinson’s (2021, June 9) retrieved June 9, 2021 from https://medicalxpress.com/news/2021-06-gut-inflammation- clues-mitigating-parkinson.html
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