Researchers discover intestinal proteins linked to Parkinson's disease

Parkinson's disease finds its origin in the intestinal tract with nerve-killing proteins that spread in the brain, a new study shows.


The incurable condition is caused by an accumulation of a misfolded protein, called alpha-synuclein, in the brain, which leads to involuntary shaking and stiff muscles.

Tests on mice have shown that the proteins spread through the vagus nerve, which runs like a power cable from the stomach and the small intestine to the base of the brain.

Study author Professor Ted Dawson, of the Johns Hopkins University School of Medicine, said: & These findings provide further evidence of the role of the gut in Parkinson's disease, and provide us with a model to monitor progression of the disease from to study the beginning.

& # 39; This is an exciting discovery for the field and provides a target for early intervention in the disease. & # 39;

The Johns Hopkins team plans to investigate which parts of the vagus nerve cause the misfolded protein to climb into the brain and explore possible mechanisms to stop it

The Johns Hopkins team plans to investigate which parts of the vagus nerve cause the misfolded protein to climb into the brain and explore possible mechanisms to stop it


The findings, published in the journal Neuron, will help researchers to develop new and more accurate models to prevent or stop the progression of the disease.

The study builds on a discovery of proteins that are clumped together in parts of the nervous system that control the gut, and in the brain, of Parkinson's patients.

After his breakthrough in 2003, the German neuroanatomist Heiko Braak hypothesized that the proteins moved like a ladder through the nerves to the brain – where they clump and cause nerve tissue to die – causing the symptoms of Parkinson's.

Dr. Hanseok Ko, from Johns Hopkins University School of Medicine, then discovered that this was consistent with the connections in the early stages of constipation.

Researchers have used two experiments to show that the proteins travel through the vagus nerve in mice from the stomach and small intestine to the base of the brain.

First, they injected 25 micrograms of synthetic misfolded alpha-synuclein that was made in the lab into the guts of dozens of healthy mice.

The brain tissues of the rodents were then sampled and analyzed at one, three, seven and ten months after injection.


These samples showed that alpha-synuclein began to build where the vagus nerve was connected to the gut and continued to spread throughout all parts of the brain.

They repeated the experiment after the vagus nerve had been surgically cut into a group of mice and injected into the guts of that group and another group without the misfolding alpha synuclein.

Seven months later, the mice with severed vagus nerves showed none of the signs of cell death found in mice with intact vagus nerve.

Dr. Dawson said the cut nerve seemed to stop the progression of the misfolded protein.

His team also examined the physical and behavioral differences between the groups of mice and a control group to see if the symptoms of the disease were present.


They used common tasks to scientifically distinguish the signs of mouse Parkinson's disease – the rodents scored from 0 to 6.

During periods of 16 hours, the Nest building tested the fine motor skills, often affected by Parkinson's disease in humans, while investigating new environments was used to determine anxiety levels.

The researchers discovered that mice that received the misfolded alpha-synuclein injection consistently scored lower on the nest structure – lower than one – while the other groups scored 3 or 4.

While most mice used the full amount of 2.5 grams of material, the group using the alpha-synuclein injection used less than half a gram of the nest material.

For the fear test, mice were placed in a large open box where a camera could follow their exploration.


Dr. Dawons said while healthy mice are normally curious, but mice affected by cognitive decline are more anxious, making them more inclined to stay at the sheltered edges of a box.

The study found that control mice and mice that had their vagus nerves cut to protect against Parkinson's disease spent between 20 and 30 minutes in the center of the box.

But the mice that received the injection, but had an intact vagus nerve, spent less than five minutes exploring the center of the box and usually moved around the borders, indicating higher levels of anxiety.

The researchers reported that this was consistent with the symptoms of Parkinson's disease.

Dr. Dawson said the findings demonstrate that blocking the transmission route through the vagus nerve can be the key to preventing the physical and cognitive manifestations of Parkinson's disease.


His team plans to investigate which parts of the vagus nerve make the misfolded protein climb to the brain and explore possible mechanisms to stop it.

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