Latest findings show that Parkinson’s disease spreads from the intestine via immune cells

Latest research shows how Parkinson’s disease spreads from the gut to the brain with the assistance of immune cells – offering a brand new potential therapeutic strategy – in a study in mice led by scientists from the UK Dementia Research Institute at UCL (University College London).

Scientists have long theorized that Parkinson’s disease may begin within the gut. It is because one in every of the primary brain areas affected on this condition is the dorsal motor nucleus of the vagus nerve, which is directly connected to the gut. Nevertheless, scientists don’t know the way the disease spreads to the brain.

The brand new study identifies a key role for intestinal macrophages – a specialized immune cell that acts as a primary responder, eating or “trapping” and destroying harmful invaders – in helping toxic proteins move from the gut to the brain.

Research showed that reducing the variety of intestinal macrophages in mice resulted in reduced spread of toxic protein and improvement in motor symptoms. The study, published within the journal and funded by the Chan Zuckerberg Initiative, suggests a brand new potential therapeutic approach for Parkinson’s that might allow intervention long before the onset of motor symptoms.

Previous research has found that between 50 and 90% of Parkinson’s patients had intestinal symptoms long before their movement symptoms appeared, similar to chronic constipation that occurred a long time before diagnosis. Depending on where the disease begins, patients are divided into “body-first” and “brain-first,” with the previous accounting for about two-thirds of individuals affected by Parkinson’s.

In the brand new study, scientists isolated misfolded alpha-synuclein, the toxic protein involved in Parkinson’s, from the brains of people that had died of Parkinson’s. They introduced tiny amounts of patient-derived alpha-synuclein into the small intestines of mice and tracked its spread from the intestines to the brain.

They showed that intestinal macrophages engulf alpha-synuclein and showed signs of dysfunction of their lysosomal systems, that are chargeable for breaking down the cell’s waste material.

The researchers found that the macrophages then gave a signal T cellsthat are a part of the body’s adaptive immune response. These “gut-controlled” T cells then migrate from the gut to the brain.

When the researchers reduced the variety of intestinal macrophages before injecting alpha-synuclein into the small intestine of mice, they found that this resulted in reduced levels of toxic alpha-synuclein within the brain in comparison with healthy controls (mice in a comparison group) – suggesting a possible therapeutic route: specifically targeting these immune cells and blocking them from reaching the brain.

Next, the team plans to review in additional detail how the body’s immune system negatively affects the brain and whether this might be used to develop recent drug targets. You will even explore how markers could be exploited inflammation within the blood as an early diagnosis of Parkinson’s.

Our study shows that immune cells aren’t bystanders in Parkinson’s disease; These intestinal macrophages respond, albeit in a dysfunctional manner. This represents a chance to take into consideration how we will strengthen the function of the immune system and these cells in order that they respond properly and help slow or stop the spread of disease.”

Dr. Soyon Hong, co-lead creator and group leader on the UK Dementia Research Institute at UCL

Co-lead creator Dr. Tim Bartels, group leader on the UK Dementia Research Institute at UCL, said: “Neurodegenerative diseases develop slowly over a long time. If we understand how Parkinson’s develops within the body, we could develop easy blood tests to screen for it and supply diagnosis long before brain damage begins. The flexibility to detect and treat Parkinson’s before it even reaches the brain could have a big impact on those affected.”