Discovered which neurons are killed by Parkinson’s disease: potential breakthrough therapies

Analysis of the brain cells of deceased people identified the specific neurons killed by Parkinson’s disease. Because it’s a turning point.

For the first time, nerve cells (neurons) that die from Parkinson’s disease, a neurodegenerative disorder characterized by tremors, cognitive decline, and motor/balance difficulties, have been identified. These cells have been identified in the lower part of the dorsal part of the substantia nigra, the pars compacta, an area of ​​the brain where there is a high density of dopaminergic neurons. They are cells specialized in the production of dopamine, a neurotransmitter involved in multiple functions, from behavior to cognition, including sleep, mood, movement, sexual satisfaction, and more. Knowing which specific neurons are affected by Parkinson’s disease may lead to innovative and more effective treatments for the widespread disease.

A research team from Harvard University’s Broad Institute and the Massachusetts Institute of Technology (MIT), working closely with colleagues from the Department of Psychiatry at Massachusetts General Hospital in Boston, has identified the exact nerve cells that are killed by Parkinson’s disease. The scientists, led by Professor Evan Z. Macosko, a researcher at the Stanley Center for Psychiatric Research at American University, came to their conclusions after analyzing and comparing brain tissue samples from eighteen people who died; ten people with Parkinson’s disease and dementia with Lewy bodies (another neurodegenerative disease with Parkinson’s-like symptoms) and eight people who died without these diseases. Altogether, Professor Macosko and his colleagues analyzed more than 22,000 brain cells.

By examining cell gene activity, the researchers identified ten different subtypes of dopaminergic neurons in the substantia nigra pars compacta or Snpc (the substantia nigra or Sommering’s substantia nigra is located between the midbrain and the forebrain and is divided into the superior compacta and ventral pars reticulata ). A specific group of these neurons, characterized by expression of the AGTR1 gene, is most commonly absent in the brains of people with Parkinson’s disease and dementia with Lewy bodies. These specific neurons also had the highest expression (upregulation) of genes associated with the risk of developing Parkinson’s disease and cell death, namely TP53 and NR2F2; This is why it is believed that they are so vulnerable to the degenerative process triggered by the disease. Put simply, they are the most vulnerable neurons and the first to die in patients with Parkinson’s disease.

Finding out which nerve cells are involved in neurodegenerative diseases can help scientists to find more targeted and effective therapy. These neurons could, for example, be developed in the laboratory from stem cells and allow scientists to test ad hoc drugs or even be used in regenerative medicine. The study of this subtype of neurons could represent a turning point in the treatment of not only Parkinson’s disease but also related diseases. Details of the research, “Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease,” were published in the authoritative journal Nature Neuroscience.

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