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Scientists discover brain cells “highly susceptible” to Parkinson’s disease

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Parkinson’s disease is a progressive neurological illness marked by uncontrollable movements such tremors, speech difficulties, and balance issues that get worse with time. It is caused by injury to the nerve cells that produce dopamine, a chemical messenger involved in mood and movement regulation.

Now a team of scientists has found what makes certain brain cells susceptible to death in Parkinson’s disease.

The research, led by Broad Institute neurobiologists Tushar Kamath and Abdulraouf Abdulraouf, examined brain cells from patients who had died from Parkinson’s disease or dementia to those who had not.

What they discovered was a subset of cells that were “particularly vulnerable” to degeneration and could be good candidates for treatment. The research also revealed how hereditary risk expresses itself in Parkinson’s disease.

Parkinson’s disease is a progressive neurological illness that is marked by uncontrollable movements such as tremors, speech difficulties, and balance problems that progressively deteriorate over time. It is caused by injury to the nerve cells that produce dopamine, a chemical messenger involved in mood and movement regulation.

A pathological feature of Parkinson’s disease is the loss of dopaminergic neurons in the substantia nigra, a portion of the midbrain. While not all dopaminergic brain cells die, we don’t yet know what chemical characteristics make some neurons more disease-prone than others.

The researchers behind this work wanted to isolate and map thousands of individual neurons from the brains of persons who had died from Parkinson’s disease or dementia with Lewy bodies, a less well-known form of dementia that can develop alone or in combination with other brain illnesses.

Kamath and colleagues studied 22,000 brain cells extracted from human brain tissue samples of 10 persons who died of Parkinson’s disease or dementia with Lewy bodies, as well as eight people who were not affected by either ailment.

The scientists identified ten unique subtypes of dopamine-producing neurons in the substantia nigra, each distinguished by their gene activity profiles, by measuring the levels of gene activity in single cells.

However, one type of dopaminergic neuron stood out as being substantially absent in Parkinson’s disease patients’ brains.

They discovered that biochemical pathways connected to cell death in other neurodegenerative disorders were accelerated in this particular type of dopaminergic neurons, and they located where the cells typically reside: in the substantia nigra pars compacta.

Furthermore, this fraction of neurons exhibited the highest expression of genes linked to Parkinson’s disease, which could explain their particular vulnerability.

In other words, Kamath and colleagues argue in their research that established genetic risk factors for Parkinson’s disease may be acting on “the most vulnerable neurons that influence their survival.”

It is crucial to highlight, however, that Parkinson’s disease and dementia with Lewy bodies are two distinct disorders with some similarities: dopaminergic neurons in the midbrain are lost, abnormal protein clumps called Lewy bodies form inside cells, and patients frequently experience the same triad of motor movement impairments.

In light of these parallels, Ernest Arenas, a molecular neurobiologist at the Karolinska Institute, argues in a commentary accompanying the article that the new study “provides valuable information on common alterations in these two diseases.”

However, because of the small number of patients studied, some disease-specific modifications may be under-represented and unreported, he warns.

However, given that we know more about the cells that are most susceptible to Parkinson’s disease and what makes them tick, researchers may build them in the lab by reprogramming skin cells into pliable stem cells, and then into the sorts of brain cells identified by Kamath and colleagues.

This lengthy procedure could enable researchers to investigate the illness’s genetic underpinnings, assess prospective medication candidates, and potentially investigate the possibility of regenerative medicine for Parkinson’s disease.

Arenas adds that combining data from single-cell sequencing studies like this one with existing imaging data, tissue pathology investigations, and genomic analysis might assist to deepen our understanding of Parkinson’s disease’s defining traits.

“This is a critical task, as our capacity to identify markers and actionable targets for [Parkinson’s disease] will determine our capacity to develop novel therapeutics for this devastating disorder,” he adds.

The research appeared in Nature Neuroscience.

Image Credit: Getty

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