When the first symptoms of Parkinson’s disease are experienced by a patient, the disease has been evolving for a long period, and the patient might already have lost half of a certain kind of nerve cells in the brain.
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Thus, scientists are keen on comprehending what occurs to such brain cells before they turn into damaged ones and die.
“You want to treat this disease early,” states Helle Bogetofte Barnkob, who is actually qualified as a medical doctor but now does research at the Department of Biochemistry and Molecular Biology.
Dopamine-Containing Nerve Cells Die
She is now at the Oxford Parkinson’s Disease Center at Oxford University in England, where she studies stem cells from Parkinson’s patients. She is also the lead author of a new scientific study published in Cell Reports. The other SDU authors are Martin Røssel Larsen, Pia Jensen, Sissel I. Schmidt, Mike B. Barnkob, and Morten Meyer, whereas the remaining author group is from the Oxford Parkinson’s Disease Center.
The scientific article of the team offers a new point of view into how the dopamine-containing nerve cells that are specifically impacted in Parkinson’s act. In Parkinson’s, such nerve cells die, and in some time, it results in an extreme dopamine deficiency.
Dopamine, a signaling substance, comes with two overarching roles: one is to control humans’ emotions and mood, and the other is to aid in regulating humans’ motor function and thereby mobility. Parkinson’s patients go through tremors as the nerve cells with dopamine significant for motor operation start dying. Besides, they also come with an increased threat of depression, among other conditions.
Cannot Form Nerve Extensions
For the research, the dopamine-containing nerve cells are developed by the team from stem cells that are taken from healthy individuals and Parkinson’s patients for control purposes. Through wide-ranging examinations of proteins, which are the building blocks of nerve cells, the research group identified certain vital differences in their capacity to make nerve extensions.
While the nerve cells are healthy, they create extensions that make connections and convert dopamine from one nerve cell to another. It was found that nerve cells from Parkinson’s patients have a considerably poorer capacity to make these extensions.
Helle Bogetofte Barnkob highlights that the findings of the research were done in a lab and that it might not essentially happen 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.”
Helle Bogetofte Barnkob, Department of Biochemistry and Molecular Biology, University of Southern Denmark
Medication Makes the Cells Better
Because the responsible nerve cells stay deep within the brain, scientists cannot access them or examine them as the disease grows. Nerve cells produced from stem cells of Parkinson’s patients are thus the closest they can simultaneously come to seeking a Parkinson’s-affected cell.
Part of the study was performed at the Oxford Parkinson’s Disease Center, where there is a huge cell bank of stem cells from healthy individuals and Parkinson’s patients. The second chief part of the study was conducted at SDU in Odense, where innovative, proteome-analyzing equipment can offer scientists with knowledge about thousands of proteins and protein modifications concurrently.
The study group also examined if they could do something to cure the sick nerve cells, and they discovered that a few kinds of medication make the cells better at creating nerve extensions. They discovered that the nerve cells in the Petri dishes reacted well to a substance employed to cure the rare Gaucher’s disease: They turned better at creating nerve extensions.
Is it the Same for Patients with Sporadic Parkinson’s?
The substance functions by increasing the alleged GBA enzyme, which is significant for the maintenance work of the cell. The most common genetic risk factor for Parkinson's is the mutations in the GBA gene. The stem cells of patients involved in the research all came from Parkinson’s patients with a mutation in the GBA gene.
The ratio of genetically determined and thus hereditary cases of Parkinson’s is around 10%. This implies that the vast majority—a maximum of 90% of all Parkinson’s cases—are infrequent owing to a combination of genetic risk and environmental factors.
Currently, Helle Bogetofte Barnkob is examining nerve cells produced from stem cells from patients with intermittent Parkinson’s. She wants to study, among other things, if the same things occur in those cells with the mutation in the GBA gene, like in those with irregular Parkinson's.
Parkinson’s happens in 1% of the population after the age of 50 years. The occurrence is the highest in people with more than 70 years of age.
Barnkob, H. B., et al. (2023). Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson's disease GBA-N370S dopamine neurons. Cell Reports. doi.org/10.1016/j.celrep.2023.112180.