Research press release


Nature Neuroscience

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

ヒトの脳試料を調べた結果、パーキンソン病において選択的に消失するドーパミン放出ニューロンの特定のサブタイプが見つかった。この研究結果を報告する論文が、Nature Neuroscience に掲載される。


今回、Evan Macoskoたちは、ヒトの脳試料からドーパミンニューロン(合計2万2048個)を単離し、その遺伝子発現を測定した結果、ドーパミンニューロンのサブタイプ(10種類)を発見した。そして、パーキンソン病患者と非罹患者の測定結果を比較したところ、黒質緻密部の腹側に位置し、AGTR1遺伝子の発現によって特定可能なサブタイプが、パーキンソン病患者の脳内で消失していることが多かった。これは、このニューロンのサブタイプがパーキンソン病に対して最も脆弱なことを示唆している。また、このサブタイプは、パーキンソン病の発症リスクを生み出す遺伝子の発現が最も高く、このことによって脆弱性を説明できる可能性がある。


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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