Parkinson's Disease(PD) may originate in the Gut, New Study Shows

Researchers find that protein clumps can travel up from the gut to the brain.

Parkinson's Disease(PD) may originate in the Gut, New Study Shows
Approximately 60,000 Americans are diagnosed with PD each year.

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

Nearly one million are living with Parkinson's disease (PD) in the U.S., which is more than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig's disease (or Amyotrophic Lateral Sclerosis).

Approximately 60,000 Americans are diagnosed with PD each year and worldwide, more than 10 million people worldwide are living with PD. Incidence of Parkinson’s disease increases with age, but an estimated four percent of people with PD are diagnosed before age 50. Men are 1.5 times more likely to have Parkinson's disease than women.

The combined direct and indirect cost of Parkinson’s, including treatment, social security payments and lost income, is estimated to be nearly $52 billion per year in the United States alone.

Medications alone cost an average of $2,500 a year and therapeutic surgery can cost up to $100,000 per person.

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.

Causes and symptoms

Doctors aren't sure of the exact cause of Parkinson's disease. They do know that if you have the illness, the trouble starts in some of your brain cells.

In an area of your brain called the substantia nigra, cells that make the chemical dopamine start to die. Dopamine has an important job to do. It acts like a messenger that tells another area of your brain when you want to move a part of your body.

When the cells that make dopamine start to die, your dopamine level drops. When it gets too low, you can't control your movements as well and you start to get Parkinson's symptoms.

No one knows what triggers the death of those cells. Scientists think it's your genes and environment working off of each other in a way we don't understand.

They can, but it's rare and only affects a small number of families. About 1 in 100 people with Parkinson's get it this way

One study, based in France, found in 2015 that men are 50 percent more likely to develop Parkinson’s disease than women overall, but the risk for women appears to increase with age.

In most people, symptoms appear at the age of 60 years or over. However in 5–10 percent of cases they appear earlier. When Parkinson’s disease develops before the age of 50 years, this is called “early-onset” Parkinson’s disease.

Symptoms of PD include tremor in the hands, a reduced sense of coordination and balance can cause people to drop items they are holding, a person’s posture may change, so that they lean forward slightly, as if they were hurrying.

Two of the more prominent symptoms of PD are a shuffling gait and the Parkinson's Mask where facial expression can become fixed, due to changes in the nerves that control facial muscles.

There may also be a tremor in the voice, or the person may speak more softly than before and a loss of sense of smell can also be an early sign.

Study habits

According to the team at the California Institute of Technology, α-Syn aggregates have also been found in neurons in the intestines of people with PD and 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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Frank Racioppi
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