Photograph used for representational purpose only
| Photo Credit: Getty Images

Digestive problems, including ulcers in one’s food pipe or stomach, could increase the risk of Parkinson’s disease by 76 per cent, according to a new study.

Analysing endoscopy reports of 9,350 patients, the authors found that people having upper gastrointestinal conditions — specifically, ulcers or other types of damage to the lining of the oesophagus, stomach, or upper part of the small intestine — were far more likely to develop Parkinson’s disease later in life.

These findings, published in the Journal of the American Medical Association Network Open, add to a growing body of evidence that ageing-related or neurodegenerative disease, long thought to originate in the brain, could begin in the gut.

Gastrointestinal problems are known to be common in patients suffering from neurodegenerative disorders, the authors said.

The researchers at the Beth Israel Deaconess Medical Center, United States, said that gastrointestinal troubles experienced by patients of Parkinson’s disease often appear up to two decades before symptoms such as tremors or stiffness in arms or legs, which interfere with one’s movement and are usually the grounds for diagnosis.

They said that digestive issues can involve constipation, drooling, difficulty in swallowing and a delayed emptying of the stomach. Constipation and difficulty in swallowing were strong risk factors related with a more than doubling of Parkinson’s disease risk, the authors said.

One of the possible biological mechanisms underlying these relationships between the gut and risk of Parkinson’s disease could be problems in regulating dopamine, a brain chemical known to play a key role in digestion, they said.

The authors also proposed that gastrointestinal conditions could trigger the building up of the protein ‘alpha-synuclein’, which is how Parkinson’s disease presents in the brain.

Future research could help understand these mechanisms better, they added.

Mitochondria are dynamic. They constantly shift in size, number and location, traveling between many different parts of the cells to meet different demands. Photograph used for representational purposes only
| Photo Credit: Getty Images/iStockphoto

In 1817, a British physician named James Parkinson published An Essay on the Shaking Palsy, describing for the first time, cases of a neurodegenerative disorder now known as Parkinson’s disease. Today, Parkinson’s disease is the second most common neurodegenerative disease in the U.S. It affects about 1 million Americans and more than 10 million people worldwide.

The signature shaking in patients with the disease is the result of dying brain cells that control movement. To date, there are no treatments available that can stop or slow down the death of those cells.

We are researchers who studyParkinson’s disease. For over a decade, our lab has been investigating the role that mitochondria – the powerhouses that fuel cells – play in Parkinson’s.

Our research has identified a key protein that could lead to new treatments for Parkinson’s disease and other brain conditions.

Mitochondrial dynamics and neurodegeneration

Unlike actual power plants, which are set in size and location, mitochondria are rather dynamic. They constantly shift in size, number and location, traveling between many different parts of the cells to meet different demands. These mitochondrial dynamics are vital to not only the function of mitochondria but also the health of cells overall.

A cell is like a factory. Multiple departments must seamlessly work together for smooth operations. Because many major processes interconnect, impaired mitochondrial dynamics could cause a domino effect across departments and vice versa. Collective malfunction in different parts of the cell eventually leads to cell death.

Emerging studies have linked imbalances in mitochondrial processes to different neurodegenerative diseases, including Parkinson’s disease. In many neurodegenerative disorders, certain disease-related factors, such as toxic proteins and environmental neurotoxins, disrupt the harmony of mitochondrial fusion and division.

Impaired mitochondrial dynamics also take down the cell’s cleaning and waste recycling processes, leading to a pileup of toxic proteins that form harmful aggregates inside the cell. In Parkinson’s, the presence of these toxic protein aggregates is a hallmark of the disease.

Targeting mitochondria to treat Parkinson’s

Our team hypothesized that restoring mitochondrial function by manipulating its own dynamics could protect against neuronal dysfunction and cell death.

In an effort to restore mitochondrial function in Parkinson’s, we targeted a key protein that controls mitochondrial dynamics called dynamin-related protein 1, or Drp1. Naturally abundant in cells, this protein travels to mitochondria when they divide into smaller sizes for higher mobility and quality control. However, too much Drp1 activity causes excessive division, leading to fragmented mitochondria with impaired function.

Using different lab models of Parkinson’s, including neuronalcell cultures and rat and mice models, we found that the presence of environmental toxins and toxic proteins linked to Parkinson’s, cause mitochondria to become fragmented and dysfunctional. Their presence also coincided with the buildup of those same toxic proteins, worsening the health of neuronal cells until they eventually started dying.

We also observed behavior changes in rats that impaired their movements. By reducing the activity of Drp1, however, we were able to restore mitochondria to their normal activity and function. Their neurons were protected from disease and able to continue functioning.

In our 2024 study, we found an additional benefit of targeting Drp1.

We exposed neuronal cells to manganese, a heavy metal linked to neurodegeneration and an increased risk of parkinsonism. Surprisingly, we found that manganese was more harmful to the cell’s waste recycling system than to its mitochondria, causing buildup of toxic proteins before mitochondria became dysfunctional. Inhibiting Drp1, however, coaxed the waste recycling system back into action, cleaning up toxic proteins despite the presence of manganese.

Our findings indicate that inhibiting Drp1 from more than one pathway could protect cells from degeneration. Now, we’ve identified some FDA-approved compounds that target Drp1 and are testing them as potential treatments for Parkinson’s.

Rebecca Zhangqiuzi Fan is Post-doctoral Research Associate in Environmental Health Sciences, Florida International University

Kim Tieu is Professor of Environmental Health Sciences, Florida International University

This article is republished from The Conversation under a Creative Commons license. Read the original article here