Is this how Parkinson's Disease invades from the gut?

A route through which Parkinson's Disease may be triggered in the intestine and then access the brain has been uncovered by US researchers.
15 June 2017


An enteroendocrine cell expressing alpha-synuclein


A route through which Parkinson's Disease may be triggered in the intestine and then access the brain has been uncovered by US researchers. 

Parkinson's Disease is common; around the world about 10 million people are currently suffering with the condition, which classically produces the a rhythmic tremor, difficulty initiating movements and worsening muscle rigidity. Later, the condition also leads to cognitive impairment.

Parkinson's symptoms occur when the population of nerve cells that secrete the signalling chemical dopamine are lost from a discrete region of the brain. But why these nerve cells are selectively vulnerable has never been explained.

Some researchers have blamed heredity, others have pointed the finger at environmental poisons and toxins, or drugs. Many blame bad luck. But in 2016 scientists in California surprised the world with the announcement that Parkinson's Disease might begin in the gut.

A team at Caltech, led by Sarkis Mazmanian, had shown that mice prone to developing a rodent equivalent of Parkinson's only did so if their intestines were colonised with bacteria.

So-called "germ free" mice with the same Parkinson's preponderance but reared in a sterile environment did not succumb. Colonising the mice with bacteria from the guts of Parkinson's patients, but not healthy humans, also triggered the disease, strongly implicating the bacteria, and possibly the short chain fatty acids they secrete, in the development of the disease.

What remains unclear, however, is how the condition is transferred from the gut to the nervous system. Enter Duke University researcher Rodger Liddle.

This week he and his team have published a paper in the Journal of Clinical Investigation Insight in which they claim to have found at least one way to link the gut microbiome with the nervous system.

Liddle and his team have been studing a population of cells that live in the intestinal lining. They're called enteroendocrine cells or EECs and one of their roles is to sample the gut contents and, in response, release signals such as hormones, including into the blood, so the body can respond to what's happening in the intestine.

However, Liddle's group have discovered that they also connect to nerve cells in the gut wall. And in their present paper, in which they studied both cultured EECs as well as human bowel biopsy specimens, they have found that these cells also express a key protein called alpha-synuclein.

This protein has been shown to build up inside nerve cells destined to die from Parkinson's. Perhaps, Liddle speculates, some toxic milieu in the gut, brought about by the microbes that live there, trigger the alpha-synuclein in the EECs to begin to aggregate into the nerve-toxic form.

This, he suggests, could pass into the adjacent connected nerve cells, which then ferry the pathological protein up to the brain.

The team don't think that it's a coincidence that patients with Parkinson's Disease frequently also develop bowel problems such as constipation, sometimes years before they show any neurological signs of the disease. EECs exert powerful effects on gut motility and it's possible, the team say, that these cells are also adversely affected in Parkinson's Disease.

If that's true, it may even be possible to diagnose Parkinson's in future using a bowel biopsy.


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