Dealing with Parkinson's disease, from the "intestines"?

(PD) is a neurodegenerative disease that affects millions of older people worldwide. The main manifestations of patients are limb tremors, stiffness, impaired motor function, etc. when still. But doctors have long found that many PD patients often have gastrointestinal disorders, such as constipation, before they experience movement disorders.May Parkinson's disease originate in the gastrointestinal tract? Further speculation comes from the study of synactinopathy. In some brain regions of PD patients, this protein folds incorrectly, and large amounts of insoluble α-Syn proteins aggregate within cells, causing nerve cell death. Some evidence suggests that, in addition to the brain, α-Syn aggregation occurs in the stomach, hexa finger intestine and colon, and is likely to begin early in the disease process.In animal experiments, scientists have also observed that the pathological α-Syn protein can spread from the gastrointestinal tract to the brain through interconnected nerves, causing a variety of PD-related symptoms.If the destructive protein that causes PD originates in the intestinal neurons, focusing on the gastrointestinal tract not only helps to make an earlier diagnosis, but may also slow or avoid disease progression by removing protein aggregation as early as possible.Recently, a team led by Professor Viviana Gradinaru of the California Institute of Technology tested this hypothesis in mouse experiments. They found that abnormal proteins in the gastrointestinal tract not only spread to the brain causing pathological changes, but also easily affected the motor function of older mice. Strengthening the removal of abnormal proteins from the gastrointestinal tract can help improve symptoms. The results were published in The Nature sub-journal Nature Neuroscience.For the study, scientists injected susceptible syn-Syn fibrogens into the α's tidal intestinal walls. Results As they predicted, over the next few months, protein aggregates gradually spread upward, affecting PD-related brain regions such as the brain trunk and middle brain.Notable, mice of different ages were affected differently. Relatively young adult mice did not develop movement disorders as a result, and pathoproteins decreased over time, while older mice (about 16 months old) showed symptoms such as insufficient stomach power and abnormal detocation, as well as increasing movement disorders.Why do these protein aggregates cause movement disorders in older animals, while younger animals are not affected? The researchers speculate that this may be α the mechanism of eliminating the protein-Syn protein.For example, a protein called GCase helps break down the α-Syn protein. As the enzyme's function is impaired, α-Syn protein begins to aggregation. The amount of GCase produced in older mice was significantly lower than in younger mice. "As you get older, you become inefficient in dealing with pathogens, including misfolded proteins. Parkinson's disease may be like this. Lead author Dr. Collin Challis said.So the team designed a method to help the intestinal nerves process protein aggregation. They used AAV-PHP.S, a modified vector based on adeno-related viruses (AAVs), to deliver genes that encode GCase. This designed gene vector, harmless to animals, is injected into the bloodstream and can be effectively absorbed by extrinsic neurons, which express GCase specifically within the gastrointestinal neurons for a long time.The results showed that with the addition of GCase, overextended pathological α-Syn mice had reduced protein aggregation in intestinal neurons and improved gastrointestinal function.“ Our results show that the gastrointestinal symptoms in mice can be alleviated by the AAV delivery (encoded GCase) gene. It also highlights the important point that, in addition to the brain, periconal neurons are also a valuable target for dealing with PD. Professor Gradinaru said. (Academic latitude and longitude)