All New Insights About Dying Cells in Parkinson’s Disease

When a patient first notices signs of Parkinson’s disease, the disease has already progressed and the patient may have lost half of a certain type of nerve cell in the brain.
As a result, researchers are working to figure out what happens to these brain cells before they become injured and die.

“You want to treat this disease early,” says Helle Bogetofte Barnkob, who is originally trained as a medical doctor but now researches at the Department of Biochemistry and Molecular Biology, University of Southern Denmark.

She is currently based at Oxford University’s Oxford Parkinson’s Disease Center in England, where she investigates stem cells from Parkinson’s patients. She is also the lead author of a recent scientific study that was published in Cell Reports. Martin Rssel Larsen, Pia Jensen, Sissel I. Schmidt, Mike B. Barnkob, and Morten Meyer are the other SDU authors, and the rest of the author team is from the Oxford Parkinson’s Disease Center.

The team’s scholarly paper sheds fresh light on how dopamine-containing nerve cells, which are notably impaired in Parkinson’s disease, function. These nerve cells die in Parkinson’s disease, resulting in severe dopamine shortage over time.

Dopamine is a signaling molecule that has two major functions: one is to govern our mood and emotions, and the other is to help control our motor function and hence our mobility. Tremors occur in Parkinson’s patients as dopamine-containing nerve cells, which are essential for motor function, begin to die. They are also at a higher risk of depression, among other disorders.

For the study, the researchers created dopamine-containing nerve cells from stem cells from Parkinson’s sufferers and healthy persons. The scientists discovered several critical differences in the ability of nerve cells to produce nerve extensions after conducting detailed examinations of the nerve cells’ building components, proteins.

When nerve cells are healthy, they develop extensions that link to other nerve cells and transport dopamine from one to the other. Parkinson’s sufferers’ nerve cells were shown to have a much lower ability to produce these extensions.

Helle Bogetofte Barnkob emphasizes that the team’s findings were made in a laboratory and that it may not necessarily occur in a human brain: “We work with nerve cells in a petri dish, and we do not know if the same thing happens in a brain. But we can say that nerve cells developed from Parkinson’s patients’ stem cells cannot form extensions as well as those from healthy patients,” she explains.

Because the key nerve cells are located deep within our brain, researchers are unable to access or examine them as the disease progresses. Nerve cells derived from Parkinson’s patients’ stem cells are thus the closest they can now get to studying a Parkinson’s-affected cell.

Part of the research was done at the Oxford Parkinson’s Disease Center, which has a huge cell bank of stem cells from Parkinson’s sufferers and healthy people. The second critical component of the study was conducted at SDU in Odense, where advanced proteome-analyzing technology can supply researchers with information on hundreds of proteins and protein changes at the same time.

The researchers also looked into whether they might treat the ill nerve cells, and they discovered that a specific sort of medicine improves the cells’ ability to generate neuron extensions. They discovered that nerve cells in petri dishes responded well to a chemical used to treat the rare condition Gaucher’s disease: they improved their ability to generate neuron extensions.

The chemical acts by increasing the activity of the GBA enzyme, which is essential for cell upkeep. The most prevalent genetic risk factor for Parkinson’s disease is a mutation in the GBA gene. The patient stem cells used in the study were all derived from Parkinson’s disease patients who had a mutation in the GBA gene.

About 10% of Parkinson’s disease cases are genetically determined and so inherited. This means that the vast majority of Parkinson’s cases—up to 90% of all cases—are sporadic and caused by a combination of environmental and genetic risk factors.

Helle Bogetofte Barnkob is presently researching nerve cells derived from sporadic Parkinson’s patients’ stem cells. She wants to see if the same things happen in the cells of people who have the GBA gene mutation as in people who have sporadic Parkinson’s.

Parkinson’s disease affects 1% of people over the age of 50. The prevalence is greater in adults over the age of 70.

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