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Animal study presents best evidence to date that Parkinson's begins in the gut


An important and rigorous new animal study led by scientists at Johns Hopkins University has demonstrated how the misfolded proteins thought to cause Parkinson's disease may originate in the gut, and travel up to the brain via the vagus nerve. This research builds on a compelling body of evidence pointing to a gut-brain connection in the disease and hints at possible new treatment pathways.

Parkinson's disease is characterized by the progressive cell death of the brain's dopamine-secreting neurons that is believed to be caused by the aggregation of spherical misfolded clumps of the protein alpha-synuclein. These toxic protein aggregates are often referred to as Lewy bodies.

For several decades scientists have known these Lewy bodies could be found in the gastrointestinal tracts of Parkinson's disease patients, but it wasn't until a series of influential papers were published in the early 2000s that a strong gut-brain hypothesis was put forward. German scientist Heiko Braak and his team hypothesized the disease originated in the gut, and the damaging Lewy bodies subsequently traveled up into the brain via the vagus nerve. The Braak hypothesis, as it is now known, is still a divisive idea in the field of Parkinson's research, with as many skeptics as believers.

One of the first experimental challenges in verifying the Braak hypothesis is of course establishing whether Lewy bodies can actually spread directly from the gut to the brain. A 2014 rat study effectively demonstrated this spread is indeed possible, but this new Johns Hopkins research is the most rigorous evidence produced to date, demonstrating that not only can these misfolded proteins move from the gut to the brain, but that spread can also induce key pathological signs of Parkinson's disease.

The study began by injecting synthetic misfolded alpha-synuclein into the guts of healthy mice and tracking those animals for 10 months. Analyzing brain tissue at several points over the 10-month period revealed the alpha-synuclein first aggregated at the point the vagus nerve connected to the gut, and then eventually spread throughout the brain. Even more interesting, the spread of the alpha-synuclein proteins up into the brain was halted when the animals' vagus nerve was severed.

Route of Parkinson's disease-causing protein propagation in mice

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