Experiments in mice show transmission of nerve-killing protein from the gut into the brain

In experiments in mice, Johns Hopkins Medicine researchers say they have found additional evidence that Parkinson’s disease originates among cells in the gut and travels up the body’s neurons to the brain. The study, described in the June issue of the journal Neuron, offers a new, more accurate model in which to test treatments that could prevent or halt Parkinson’s disease progression.

These findings provide further proof of the gut’s role in Parkinson’s disease, and give us a model to study the disease’s progression from the start.
Ted Dawson, M.D., Ph.D, director of the Johns Hopkins Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

Parkinson’s disease is characterized by the buildup of a misfolded protein, called alpha-synuclein, in the cells of the brain. As more of these proteins begin to clump together, they cause nerve tissues to die off, leaving behind large swaths of dead brain matter known as Lewy bodies. As brain cells die, they impair a person’s ability to move, think or regulate emotions.

The new study builds off observations made in 2003 by German neuroanatomist Heiko Braak that showed people with Parkinson’s disease also had accumulations of the misfolded alpha-synuclein protein in the parts of the central nervous system that control the gut. The appearance of these neuron-damaging proteins is consistent with some early symptoms of Parkinson’s disease, which include constipation, says Hanseok Ko, Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine. Braak hypothesized that Parkinson’s disease advanced up the nerves connecting the gut and the brain like going up a ladder.

Overall, the results of this study show that misfolded alpha-synuclein can be transmitted from the gut to the brain in mice along the vagus nerve, and blocking the transmission route could be key to preventing the physical and cognitive manifestations of Parkinson’s disease.

This is an exciting discovery for the field and presents a target for early intervention in the disease
Ted Dawson.

Next, the researchers say, they plan to explore what parts of the vagus nerve allow the misfolded protein to climb to the brain, and to investigate potential mechanisms to stop it.

 

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