Link Between Intestinal Inflammation And Neurological Problems Explained

Bowel problems are an early symptom of both Parkinson’s disease and irritable bowel syndrome. The protein LRRK2 (leucine-rich repeat kinase 2) has been genetically linked to both conditions, but the exact mechanism was unknown until now. Neuroscientists at KU Leuven show that the presence of mutant LRRK2 in immune cells causes an increased inflammatory response in the large intestine, which in time can also lead to inflammation in the brain and thus contribute to neurodegeneration such as in Parkinson’s disease.

It has been known for several years that the intestines can have an important influence on the functioning of the brain. The so-called ‘gut-brain axis’ is therefore an important new avenue for neuroscientists in research into neurological disorders such as Parkinson’s disease, which affects approximately 10 million people worldwide every year.

Researchers at KU Leuven, led by Professor Veerle Baekelandt, unraveled the central role for the protein leucine-rich repaet kinase 2, or LRRK2, in both the disease course of irritable bowel syndrome and Parkinson’s disease.

Mutation in LRRK2
Previous research had shown that one particular mutation in LRRK2 is the most important genetic cause of Parkinson’s disease. “We examined mice with the same mutation and saw that they showed an increased inflammatory response in the large intestine. Through a bone marrow transplant, we were able to demonstrate that the LRRK2 in immune cells was responsible for this. When we gave medication that blocks the function of LRRK2, the inflammation decreased,” explains Professor Baekelandt. “Conversely, if the inflammation persists for a longer period of time, the mutated immune cells can infiltrate the brain and contribute to an inflammatory response in the brain as we see in patients suffering from Parkinson’s disease.”

Reduce inflammation with medication
The researchers succeeded in combating intestinal inflammation by means of medication that blocks the action of LRRK2. “From this study we learn that LRRK2 is an important factor in the course of the disease by acting on the immune response,” Professor Baekelandt continues. “Clinical studies are currently underway in Parkinson’s patients with drugs that block LRRK2, but these results show that people with irritable bowel syndrome could also be helped with this.”