Scientists have identified brain cells that die in Parkinson's disease

Scientists have identified brain cells that die in Parkinson’s disease

Scientists have identified the specific brain cells that die in Parkinson’s disease and discovered what makes them so weak.

The team, led by neurobiologists Tushar Kamath and Abdul-Raouf Abdul-Rauf of the Broad Institute, studied brain cells from individuals who died of either Parkinson’s disease or dementia, compared to people unaffected by either disorder.

What they found was a group of cells ‘highly susceptible’ to degeneration, which could also be Leading candidates for therapeutic intervention. The study also highlights the How likely genetic risks to produce Parkinson’s disease manifest.

Parkinson’s disease is A progressive neurodegenerative disease characterized by uncontrollable movements such as tremors, speech difficulties and balance problems that get worse over time. It is caused by damage to nerve cells that produce dopamine, a chemical messenger that regulates mood and body movements.

Loss Dopaminergic neurons in a part of the midbrain called the substantia nigra are the hallmark pathological feature of Parkinson’s disease. While not all dopaminergic brain cells die, we do not have a solid understanding of the molecular features that make some neurons more susceptible to disease than others.

The team of scientists behind this latest study set out to isolate and map thousands of individual neurons from the brains of people who died of Parkinson’s disease or Lewy body dementia, a lesser known form of dementia that can occur alone or with other brain disorders.

Kamath and colleagues studied nearly 22,000 isolated brain cells from human brain tissue samples of ten individuals who died from either Parkinson’s disease or dementia with Lewy bodies, and eight people who were not affected by either disorder.

By measuring levels of gene activity in single cells, the team identified 10 distinct subtypes of dopamine-producing neurons in the substantia nigra, each of which can be distinguished by their gene activity profiles.

But one set of dopaminergic neurons emerged as largely missing in the brains of people with Parkinson’s disease.

Upon closer examination, they found that molecular processes associated with cell death in other neurodegenerative diseases were enhanced in this particular group of dopaminergic neurons, and they identified exactly where the cells normally reside: in the underside of the substantia nigra.

What’s more, this subset of neurons has the highest expression of genes that confer risk of Parkinson’s disease, which may explain its unique vulnerability.

In other words, known genetic risk factors for Parkinson’s disease may act on “the most vulnerable neurons that affect their survival,” Kamath and colleagues write in their paper.

It is important to note, however, that Parkinson’s disease and dementia with Lewy bodies are two different disorders that share some similar features: midbrain dopaminergic neurons are lost, abnormal clumps of proteins called Lewy bodies form within cells, and people often have Same triad of motor impairments.

In light of these similarities, the new study provides “valuable information on the alterations common in these two diseases,” writes Ernst Arenas, a molecular neurobiologist at Karolinska Institutet, in a commentary accompanying the research.

However, it may caution that some disease-specific alterations may be underrepresented and undetected due to the small number of subjects sampled.

However, now that we know more about which cells are most susceptible to Parkinson’s disease and what makes them a marker, researchers can engineer them in the lab by reprogramming skin cells — first into flexible stem cells, and then into the types of brain cells identified by Kamath. and colleagues.

This painstaking process may allow scientists to investigate genetic drivers of the disease, examine potential drug candidates, or even explore the possibility of regenerative medicine for Parkinson’s disease.

Arenas adds that integrating information from single-cell sequencing studies such as this one with existing imaging data, histopathology studies, and genetic analyzes would also help improve our understanding of the specific features of Parkinson’s disease.

“This is a mission critical, as is our ability to identify actionable markers and targets for [Parkinson’s disease] It will determine our ability to develop new treatments for this devastating disorder.”

The study was published in Natural Neuroscience.

2022-05-05 15:02:42

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