Brain cells that are linked to Parkinson's disease finally identified

By Clare Wilson

The subtype of brain cells that die in Parkinson’s disease has been discovered using a new technique that can identify which genes are active in individual cells.

We have known for decades that Parkinson’s disease, a progressive condition that results in the development of tremors and difficulties in moving, is linked with the gradual death of cells in part of the brain called the substantia nigra. The cells concerned make a signalling chemical called dopamine, involved in controlling movement – but their exact identity was unclear.

Medicines for Parkinson’s disease boost dopamine in various ways, yet their effects tend to wane over time, so better treatments are needed, says Evan Macosko at the Broad Institute of MIT and Harvard.

Macosko’s team looked at cells from the substantia nigra of eight people who didn’t have Parkinson’s and had agreed to donate their brains for research after death.

The researchers used a relatively new technique called single cell RNA sequencing, which allows cells within a tissue to be analysed individually to see which of their genes are active and producing proteins. They found there were 10 different subtypes of dopamine-producing cells within the substantia nigra.

Next, the researchers used the same technique on the brains of 10 people who had died with either Parkinson’s or a similar condition called Lewy body dementia. They found that only one of the subtypes of brain cells was reduced in number, suggesting many cells of this subtype had died while the people were alive.

There are about 100,000 of these cells in a healthy adult brain. “It’s a very small subset,” says Macosko. “It was like looking for a needle in a haystack.”

The findings should lead to a better understanding of the causes of Parkinson’s and a way to assess potential treatments, he says. If the cells are grown in a dish, new medicines could be tested on them, for instance. Some groups are also trying to develop dopamine-making cells that could be transplanted into the brains of people with Parkinson’s.

Journal reference: Nature Neuroscience, DOI: 10.1038/s41593-022-01061-1

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