JPD: targeting α - synuclein in the gut may effectively slow down the progression of Parkinson's disease

December 2, 2019 / BIOON / - recently, in a research report published in the International Journal of Parkinson's disease, scientists from Georgetown University Medical Center and other institutions found that targeting alpha synuclein in the gut can effectively slow down the progress of Parkinson's disease Photo source: University of Groningen the Netherlands The aggregation of α - synuclein produced in the intestine plays a key role in the pathogenesis of Parkinson's disease At present, researchers want to test the hypothesis that by targeting the intestinal Shenjing system with a compound that can inhibit the aggregation of α - synuclein in cells, the intestinal function can be restored in a short time and the central nervous system may be mildly slowed down Progressive deterioration of According to Michael zasloff, M.D., there is more and more research evidence that Parkinson's disease may start in the intestinal tract, and the aggregation of α - synuclein is considered to play a key role in the pathogenesis of the disease, which occurs in the intestinal nervous system (ENS System), and will go up along the peripheral nerve to the central nervous system, and eventually lead to inflammation and destruction of some brain tissues, targeting the formation of α - synuclein aggregates in the intestinal nervous system or may slow down the progress of Parkinson's disease When intestinal nerves are infected, they produce defensive proteins, and alpha synuclein is one of them, for example, in acute bacteria In children with gastrointestinal tract infection, α - synuclein is produced in the gut nervous system In children who receive intestinal transplantation and are more likely to suffer from gastrointestinal tract infection, the researchers found that intestinal neurons can produce α - synuclein at the beginning of acute viral infection, which lasts for several months, and can protect the nerve cells of the body for a long time In nerve cells, α - synuclein can envelop the invading virus and interfere with virus replication At the same time, it can also adhere itself to the small vesicles containing neurotransmitters and be released from nerve cells Once outside, it can attract protective immune cells from surrounding tissues Denise barbut, a researcher, pointed out that recent data showed that α - synuclein would be induced in the case of virus and bacterial infection, and it could also play an immune function by protecting the intestinal nervous system, and could alert the adaptive immune system of the body, so as to protect the central nervous system from being affected before pathogen infection In the case of chronic gastrointestinal infection or intestinal barrier damage, when the expression of α - synuclein exceeds its clearance ability, the neurotoxic aggregate formed by α - synuclein will gather in the intestinal nervous system and transport to the central nervous system In order to determine whether the targeted α - synuclein in intestinal neurons can help patients with Parkinson's disease, researchers conducted a clinical trial with a compound named ent-01, which is a synthetic derivative of squalamine, while ent-01 is isolated from the bile of squash The results show that ent-01 can transfer α - synuclein from nerve cell membrane and restore it In 2018, the researchers conducted a phase-2 clinical trial on 50 patients with normal electrical activity of gut neurons , researcher barbut said that the gut nervous system will not be irreversibly damaged in patients with Parkinson's disease In this study, we first clarified that it can reverse the neurodegenerative process of human body; in addition to gut symptoms, patients' motor, non motor symptoms (such as hallucinations), depression and cognitive function may benefit At present, researchers are conducting a phase 2B double-blind placebo-controlled trial on 110 patients to evaluate the therapeutic effect of oral ent-01 on patients with constipation and neurological symptoms; Parkinson's disease is a slow progressive disorder, which will affect the movement, muscle control and balance of the body, and it is also the second most common age-related neurodegenerative disease, people under 65 years old Parkinson's disease affects 3% of the population and 5% of people over 85 Original sources: barbut denisea, stolzenberg ethanb, zasloff Michael, et al Gastointerestinal immunity and alpha synuclein, Journal of Parkinson's release (2019) Doi: 10.3233/jpd-191702