Neuroscience: Neurons that selectively die in Parkinson’s disease identified

A specific subtype of dopamine-releasing neurons that is selectively lost in Parkinson’s disease has been identified in human brain samples, according to a study published in Nature Neuroscience.

Parkinson’s disease is a neurodegenerative disease characterized by slowed movement, tremors, stiffness, and impaired balance and coordination. The disease is caused by the degeneration of neurons located in a part of the midbrain known as the substantia nigra pars compacta (SNpc) that releases the neurotransmitter dopamine. Why these neurons selectively degenerate is unknown, and there is currently no treatment that slows this process down.

Evan Macosko and colleagues isolated dopamine neurons (22,048 in total) from human brain samples and measured their gene expression, leading them to discover 10 distinct subtypes of dopamine neuron. By comparing results from individuals with Parkinson’s disease to those from unaffected individuals, the authors found that one subtype — located in the ventral tier of the SNpc and identifiable by the expression of the gene AGTR1— was frequently missing in the brains of individuals with Parkinson’s disease, suggesting these neurons are most vulnerable to the disease. This subset also had the highest expression of genes that confer risk for developing Parkinson’s disease, providing a potential explanation for their vulnerability.

These results suggest that Parkinson’s disease may be caused by loss of a particular subset of dopamine neurons, rather than affecting the whole population of neurons equally. The authors conclude that, as more is learned about this subtype of neurons, it may be possible to develop treatments for Parkinson’s disease that target them specifically.

doi: 10.1038/s41593-022-01061-1

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