A recent study conducted by scientists from the Icahn School of Medicine at Mount Sinai, NY, reveals new information about the genetic link between Parkinson’s disease and inflammatory bowel disease (IBD). The study, published in Genome Medicine, confirmed the role of the gene LRRK2 in both conditions while also identifying new genes and pathways that are shared between Parkinson’s and IBD. The authors believe that understanding these common biochemical pathways could lead to new and more effective treatments for both conditions.
Parkinson’s disease is a progressive neurodegenerative disorder that impacts the brain’s substantia nigra, leading to a decrease in dopamine levels that causes symptoms such as stiffness and tremors. On the other hand, IBD affects the digestive system, causing symptoms like bloating, stomach cramps, diarrhea, and constipation. While these two conditions may seem unrelated, experts have long recognized connections between Parkinson’s and the gut. Research has indicated that individuals with IBD may have an increased risk of developing Parkinson’s later in life, prompting scientists to explore the underlying reasons for this association.
One of the key features of Parkinson’s is the presence of Lewy bodies in the brain, which are primarily composed of a protein called alpha-synuclein. It is unclear whether these protein aggregations are toxic or part of the body’s defense mechanisms. Evidence suggests that misfolded alpha-synuclein proteins may originate in the gut in response to inflammation and travel to the brain. Genetic studies have identified alterations in the LRRK2 gene as a common link between IBD and Parkinson’s, with certain variants affecting the risk of both diseases. The recent study delved into rare genetic variants to elucidate the relationships between LRRK2, IBD, and Parkinson’s.
The researchers examined genetic data from the BioMe BioBank, UK Biobank, and whole genomes of individuals with both IBD and Parkinson’s to identify the genetic variants associated with an increased risk of these conditions. While confirming the role of LRRK2 in Parkinson’s and IBD, the study also highlighted other gene variants that may contribute to these diseases. These findings suggest that despite minimal overlap between the genes associated with individual conditions and those linked to both Parkinson’s and IBD, the shared pathways provide valuable insights into potential therapeutic targets.
The study identified enriched pathways unique to IBD-Parkinson’s, such as MAPK signaling, LPS/IL-1 mediated inhibition of RXR function, and NAD signaling, which have established roles in intestinal inflammation and neuronal metabolism. The researchers also pinpointed 14 potential candidate genes, including LRRK2, for further validation in clinical settings as targets for future therapies. Understanding the roles of these genes in inflammation and autophagy could lead to the development of novel treatment strategies and drug repurposing to benefit patients with Parkinson’s and IBD.
Looking ahead, the researchers plan to explore the possibility of drug repurposing based on shared mechanisms between IBD and Parkinson’s. Previous studies have shown promising results with LRRK2 inhibitors, developed for Parkinson’s, alleviating experimental colitis, indicating potential therapeutic benefits for IBD. By optimizing existing drugs and testing them in clinical trials, researchers aim to uncover new avenues for treating both conditions. Targeting inflammation and modulating immune processes through drugs like anti-TNF therapy could be a viable approach to prevent Parkinson’s and improve outcomes for patients with IBD and Parkinson’s. Future research may focus on investigating the efficacy of anti-inflammatory agents or autophagy enhancers in managing both conditions, enhancing our understanding of how IBD and Parkinson’s interact and paving the way for more effective treatments.
