In the complex world of human health, sometimes the most unexpected connections can lead to the most groundbreaking discoveries.
Such is the case with the puzzling link between Parkinson’s disease—a neurodegenerative condition affecting the brain, and inflammatory bowel disease (IBD)—which primarily impacts the gut.
For years, experts have noticed an intriguing association between these seemingly unrelated conditions.
People with IBD appear to have an increased risk of developing Parkinson’s later in life, and gastrointestinal symptoms like constipation often precede the motor symptoms of Parkinson’s by several years.
But what could possibly connect a brain disorder with a gut disease? The answer, it seems, lies in our genes.
The LRRK2 Connection
A recent study conducted by scientists from the Icahn School of Medicine at Mount Sinai has shed new light on the genetic underpinnings of the Parkinson’s-IBD link.
The researchers analyzed genetic data from thousands of individuals and found that variants of a gene called LRRK2 play a crucial role in both conditions.
LRRK2 is no stranger to the world of Parkinson’s research. In fact, it’s the most well-established genetic link between Parkinson’s and IBD to date. Different variants of this gene can either increase or decrease the risk of both diseases.
But what exactly does LRRK2 do in a healthy individual? According to study author Meltem Ece Kars, MD, Ph.D., this gene “plays a role in transporting biochemical molecules between cells and maintaining cell components, as well as phagocytosis and autophagy, which are physiological processes to remove foreign, dysfunctional, and unnecessary substances from cells.”
Importantly, LRRK2 also plays a key role in regulating inflammation and immune processes—two factors that are pivotal in the development of both Parkinson’s and IBD
Beyond LRRK2: New Genes and Pathways
While confirming the importance of LRRK2, the Mount Sinai study also identified new genes and biochemical pathways that Parkinson’s and IBD share.
Interestingly, these shared genes are different from those that cause Parkinson’s and IBD individually, but they appear to influence similar biological processes.
The researchers detected significantly enriched pathways unique to the Parkinson’s-IBD connection, such as MAPK signaling, LPS/IL-1 mediated inhibition of RXR function, and NAD signaling. These pathways have established or suggested roles in intestinal inflammation and neuronal metabolism, providing valuable clues about the mechanisms that may link these conditions.
The Gut-Brain Axis
So, how might these genetic and biochemical connections manifest in the body? One leading theory involves the gut-brain axis, a bidirectional communication pathway between the digestive system and the central nervous system.
In Parkinson’s, a hallmark feature is the buildup of a protein called alpha-synuclein in the brain, forming structures known as Lewy bodies. Some evidence suggests that this misfolded protein may actually start its journey in the gut, in response to long-term inflammation, and eventually make its way to the brain via the vagus nerve.
As neurologist Daniel Truong, MD, explains, “The presence of alpha-synuclein in the gut’s nervous system supports the hypothesis that Parkinson’s pathology might start in the gut and spread to the brain via the vagus nerve.”
Armed with this new genetic and mechanistic understanding, researchers are hopeful that they can identify better and more effective treatments for both Parkinson’s and IBD.
The 14 genes identified in the Mount Sinai study, including LRRK2, are potential candidates for further validation in clinical settings and could be targets for future therapies. The inflammation and autophagy-related pathways uncovered in this research could also pave the way for novel therapeutic strategies.
The connection between Parkinson’s and IBD may seem surprising at first glance—but the latest research reveals that our genes hold the key to understanding this complex relationship.
By uncovering the shared genetic and biochemical pathways that underlie these conditions, scientists are opening the door to a new era of treatment.
As we continue to unravel the mysteries of the gut-brain axis and the role of genetics in disease, we move closer to a future where conditions like Parkinson’s and IBD can be effectively treated, or even prevented altogether.
P.S. Common chemicals fueling the Parkinson’s epidemic?
Sources:
https://www.medicalnewstoday.com/articles/ibd-parkinsons-disease-study-discovers-genetic-link