According to a recent publication from the Duke University School of Medicine, Dr. Rodger Liddle believes Parkinson’s disease may have origins in an unlikely place — the gut. Liddle, a professor of the school’s Department of Medicine, formulated this theory after meeting with Nobel prize winner Stanley Prusiner.
About Parkinson’s Disease
Parkinson’s disease is a degenerative disease that affects the nervous system. Parkinson’s is characterized by the atrophy and eventual death of nerve cells in the brain (neurons). As these cells weaken and die off, serious physical and neurological changes can occur. Thinking difficulties and emotional changes may become apparent. Some patients develop sleep disorders, falling asleep at inappropriate times or struggling to stay asleep at night.
Patients eventually develop physical symptoms, including episodic bouts of pain, abnormal fatigue, and problems with chewing and swallowing. Although Parkinson’s is not itself fatal, complications from physical and mental symptoms can be serious.
Could Parkinson’s Begin in the Gut?
Despite all researchers do know about Parkinson’s, no cause has been identified. Several factors are thought to be related, however, like certain genetic mutations and environmental factors. Patients with Parkinson’s develop abnormal clumps of protein inside their brain cells called Lewy bodies.
It wasn’t until relatively recently that researchers proposed a “nerve highway” between the gut and brain. For some time it was known that the gut contained a hormone called cholecystokinin (CCK) that triggered feelings of “fullness.” However, how that hormone induced a response in the brain was uncertain.
In 2014, Drs. Rashmi Chandra and Diego Bohórquez discovered a new type of cell in the gut lining of a mouse. The cell had strange properties — it contained neurofilaments (small filaments found in the cytoplasm), secretory vesicles, and lots of mitochondria. These characteristics were completely unusual for gut cells — in fact, the new cell was strongly suggested to be some kind of nerve cell.
To confirm what they both suspected, Bohórquez injected rabies into the gut of a mouse. Rabies only spreads through nerve cells. If the disease managed to spread to areas outside the gut, it would confirm that the gut contains nerve cells that link it to the rest of the body’s nervous system. Surely enough, the virus spread not long after being introduced to the gut. A complete revelation.
The new discovery prompted other researchers to reconsider the role of the gut in neurological conditions. Dr. Rodger Liddle was one. He wondered if these nerve cells might explain how mad cow disease, a prion disease, killed humans who ate ingested affected meat. Prions are misfolded proteins that proliferate rapidly, causing other proteins in contact to misfold in turn. How were proteins in the stomach wreaking havoc on the brain? Perhaps Bohórquez’s new nerve cells, called neuropods, could explain.
But the man who discovered prions, Nobel Prize laureate Stanley Prusiner, himself discouraged Liddle from pursuing the research. “When was the last time you saw a patient with mad cow disease?” Prusiner supposedly asked.
Instead, Prusiner suggested Liddle research neuropods’ role in another neurological condition — Parkinson’s. Lewy bodies, one of the defining characteristics of Parkinson’s, contain high concentrations of the protein alpha-synuclein. The alpha-synuclein is particularly densely packed and difficult for cells to break down. When Rashmi Chandra and Diego Bohórquez first researched their newly-discovered gut cells, they found that they contained a gene coding for the production of alpha-synuclein.
According to Liddle, it may not only be possible but likely that Parkinson’s begins in the gut with an over-production of alpha-synuclein that travels along the gut-nerve highway to the brain.
Much more research is required before this can be confirmed, of course. But the case for Parkinson’s beginning in the digestive tract isn’t as outlandish as it may at first sound.
What do you think of this interesting news? Does it surprise you how the body chemistry of the gut might have an impact on the brain? Share your thoughts with Patient Worthy!