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03 - 07 - 2017

Parkinson’s and intestinal infections: more evidence for a link

 

A study has revealed that a protein that causes Parkinson's disease originates from repeated infections of the intestines. Validated on several animal models, this hypothesis could soon result in a drug and better prevention of the disease.


Parkinson’s and intestinal infections: more evidence for a link
Parkinson's disease is clinically characterized by aggregates of the protein called alpha-synuclein, which disrupts the ffunction of dopamine neurons in the brain. The resulting dopamine deficiency is responsible for the main symptoms of the disease, namely motor disorders.In recent years, studies have shown a migration of alpha-synuclein molecules from the gastrointestinal tract (GI) to the brain. According to research published on the June 27 in the Journal of Innate Immunity, alpha-synuclein (αS) is released in the upper gastrointestinal tract during infections. The protein would then migrate from the GI tract to the brain via the enteric nervous system that controls the digestive organs. Thus, in situations of frequent infections of the GI tract, the brain would end up being overwhelmed with αS that the immune system could no longer eliminate, leading to Parkinson's disease. "When expressed in normal amounts following infection of the upper GI tract, αS is a good molecule, with a protective effect," says Michael A. Zasloff, co-author of the study that used biopsies harvested from patients with GI tract infections. "The nervous system located in the wall of the GI tract detects the presence of a pathogen and responds by releasing alpha-synuclein. This then attracts white blood cells to the site in question. In addition, αS released into a nerve can spread into other nerves, allowing it to have a broad protective action. "However, "too much αS, usually observed after multiple or chronic infections, becomes toxic because it submerges the nervous system, forms aggregates and chronic inflammation," the researcher explains. The resulting damage occurs both in the gastrointestinal nervous system and in the brain.Researchers have also shown that alpha-synuclein can attract immune system cells, including macrophages and neutrophils, and that this protein can activate dendritic cells that detect a pathogen and have a "sentinel" function. A discovery that comes after several studies on animals Prior to this work in patients, several studies in animal models were conducted. A study published in October 2016, conducted in rats, showed that microbiota bacteria could induce the formation of αS aggregates in the enteric nervous system and even in the brain.And earlier, in 2014, a study, again carried out in the rat, highlighted the signs conveying the migration of the alpha-synuclein from the intestinal tract to the brain. Scientists used a human brain lysate with Parkinson's disease containing αS, which they injected into the intestinal wall of rats to test their hypothesis. They demonstrated for the first time the transport of these proteins by the vagus nerve, from the intestinal wall to the brain. New data to better prevent and treat This new study tells us more about the exact role of alpha-synuclein and the reasons for its accumulation. It is therefore consistent with previous studies in animal models. It also makes sense with respect to observations made on Parkinson's patients, who often present chronic constipation and other digestive problems long before they present the first symptoms of Parkinson's disease.This work could, if confirmed in further studies, lead to changes in the prevention of Parkinson's disease, to act before the alpha-synuclein has migrated into the brain in large quantity. In addition, a clinical study on the accumulation of αS in the enteric nervous system is underway. It intends to verify the safety and tolerability of a synthetic squalamine drug candidate, ENT-01, that could alleviate constipation associated with Parkinson's disease. In animal experiments, this molecule reducs both the formation of αS aggregates and its toxicity. A therapeutic treatment for alpha-synuclein could soon be created. Hélène Bour For more information :https://gumc.georgetown.edu/news/Protein-Associated-with-Parkinsons-Disease-Linked-to-Human-Upper-GI-Tract-Infectionshttps://www.inserm.fr/thematiques/neurosciences-sciences-cognitives-neurologie-psychiatrie/dossiers-d-information/maladie-de-parkinson