Individual brain cells may hold clues to Parkinson’s disease

The study of individual brain cells that die in Parkinson’s disease may offer insights into how the disease causes damage, and pave the way for developing new treatments.

“Our hope is that if we can identify what makes dying cells vulnerable, then we can modify that with treatment,” says Neuroscience Research Australia’s Associate Professor Kay Double.

In Parkinson’s disease, cells die in a specific region of the brain called the substantia nigra. These cells control movement, so people with Parkinson’s disease often have stiff or rigid muscles and find it difficult to move freely.

We still don’t understand what causes brain cell death in Parkinson’s disease.

“There’s been a lot of work comparing the substantia nigra to other regions of the brain to find out why these cells die,” says Associate Professor Double.

“The puzzle is that only some of the cells in this region die. Some cells continue to survive even 10 or 20 years after the disease has started,” she says.

“The unique feature of what we are doing at NeuRA is comparing cells within this vulnerable region in the human brain to identify the features that differ between the cells that survive and those that die off. The fact that we are doing these studies in the human brain is important, as much of what we think we know about these cells has come from studies in other species, such as rats, where the substantia nigra is quite different.”

Associate Professor Double and research colleague Professor Glenda Halliday believe that while cells in a brain region may appear to be the same, subtle differences in the way individual cells function increases their vulnerability to the disease.

The group, including PhD student Stefanie Reyes and postdoctoral researcher Dr Eryn Werry, is looking at how effectively individual cells produce protective molecules such as growth factors, as well as how they produce and handle the neurotransmitter dopamine, a chemical which can be potentially damaging for the cell.

“Individual cell may make more or less dopamine, and that may have significant implications for cell vulnerability,” says Associate Professor Double.

The team is also looking at how these cells regulate their electrical activity and how they control iron and copper levels.

“Iron and copper are really important metals for the normal function of these cells. But too much iron or copper can be dangerous for the cell. We’re looking at how well cells regulate levels of these metals, and how well they are able to protect themselves at the same time,” says Associate Professor Double.

“There are probably very subtle differences between the cells in these areas, but they could potentially be very important,” she says.

The team’s review paper, ‘Selective cell death in neurodegeneration: Why are some neurons spared in vulnerable regions?’, was published recently in the journal Progress in Neurobiology.