Parkinson’s disease may originate in the gut, new study shows

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder, impairing the motor functions of millions of elderly people worldwide.

Often, people with PD will experience disturbances in gastrointestinal function, such as constipation, years before motor symptoms set in.

Postmortem examinations of the brains of people with PD have shown that their brain cells that control movement are littered with aggregates, or clumps, of a protein called alpha-synuclein (α-Syn).

In a new study, researchers discovered that these clumps can travel up from the gut to affect neurons in the brain—but this process depends on age.

The research was conducted by a team at the California Institute of Technology.

As α-Syn aggregates have also been found in neurons in the intestines of people with PD, some researchers hypothesize that α-Syn aggregation begins first in the nervous system of the gut.

The idea is that the protein aggregates then hop from neuron to neuron, traveling from the gut nervous system up the vagus nerve and into the brain, seeding the formation of additional aggregates along the way.

In the study, mice produce an enzyme that is able to break down these clumps, but as they get older, they may lose this ability, which could explain why PD develops most often in elderly people.

The researchers showed that injecting mice with systemic delivery vectors carrying genes that encode for this enzyme helped reduce some of the clumpings and partially restored proper gut function.

The team says the vagus nerve is a physical connection between neurons in the gut and neurons in the brain.

If these damaging protein clusters first originate in gut neurons, then doctors may be able to diagnose PD earlier and potentially use gene delivery to restore functions to the cells so that they can clean up the aggregates.

The lead author of the study is Collin Challis, a former postdoctoral scholar.

The study is published in the journal Nature Neuroscience.

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