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

By analyzing the brain cells of deceased people, the specific neurons that are killed by Parkinson’s disease have been identified. Because it’s a turning point.

For the first time, nerve cells (neurons) that die from Parkinson’s disease, a neurodegenerative disease 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 much more. Knowing which specific neurons are affected by Parkinson’s disease can 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, discovered the exact nerve cells killed by Parkinson disease. The scientists, led by Professor Evan Z. Macosko, a researcher at the Stanley Center for Psychiatric Research at American University, reached their conclusions after analyzing and comparing samples of brain tissue taken from eighteen deceased people; ten people with Parkinson’s disease and dementia with Lewy bodies (another neurodegenerative disease with Parkinson-like symptoms) and eight people who died without these diseases. In total, Professor Macosko and his colleagues analyzed more than 22,000 brain cells.

By studying levels of cell gene activity, the researchers identified ten distinct 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 superior pars compacta and ventral pars reticulata). A specific group of these nerve cells, characterized by expression of the AGTR1 gene, was found to be most frequently absent from the brains of people with Parkinson’s disease and dementia with Lewy bodies. These specific neurons also had the highest expression (upregulation) of genes linked to the risk of developing Parkinson’s disease and cell death, namely TP53 and NR2F2; for this reason, they are thought to be so susceptible to the degenerative process triggered by the disease. Simply put, 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 find specific and more effective therapy. For example, these neurons could be designed 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 not only in the treatment of Parkinson’s disease but also of related diseases. Details of the research “Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease” have been published in the authoritative scientific journal Nature Neuroscience.

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