New findings could help explain the complexity of Parkinson’s disease symptoms and point to potential new treatment pathways.
A research team at Mount Sinai Hospital has identified a previously unreported neuron type with vulnerability in Parkinson’s disease.
Writing in the publication, Medical Xpress, those behind the study say that this novel finding could help explain the complexity of the disease symptoms and direct new therapeutics development.
Parkinson’s is characterised by the loss of dopaminergic (DA) neurons in the substantia nigra, a part of the brain that helps control the body’s movements. Whether cell types beyond DA neurons in this brain region show vulnerability in Parkinson’s disease remains unclear.
Through transcriptomic profiling of more than 300,000 cells in human substantia nigra, the researchers identified cell clusters representing various neuron types, glia, endothelial cells, pericytes, fibroblasts, and T-cells, and investigated cell-type dependent alterations in gene expression in Parkinson’s disease.
A unique neuron cluster marked by the expression of RIT2, a Parkinson’s risk gene, also displayed vulnerability in Parkinson’s disease.
Researchers have now established a transcriptomic atlas of the human substantia nigra at single-cell resolution and delineated the landscape of molecular and cellular alterations in Parkinson’s disease.
The study provides a valuable resource for dissecting molecular and cellular compositions and structures of the human substantia nigra, the researchers say, but also presents an unprecedented opportunity to understand in-depth pathogenic mechanisms, identify key therapeutic targets, and develop clinical biomarkers for Parkinson’s disease.
Mount Sinai’s, Dr Zhenyu Yue, said: “Our study shows the landscape of transcriptomic signatures with cell type resolution in a brain region that is vulnerable in Parkinson’s disease. We are surprised by the finding of a neuron type with vulnerability in PD, which has never been characterized previously.”
“In addition, our study provides the opportunity to interrogate the remaining dopamine neurons at advanced disease stages and identify clues for how they are adapted and survive while the vast majority of dopamine neurons are lost.”
Dr Bin Zhang added: Equally significant is the identification of molecular alterations in different brain cell types in PD. These findings provide not only profound insights into the underlying pathogenic mechanisms but also vital therapeutic targets for PD.”
James C Beck, PhD, chief scientific officer of the Parkinson’s Foundation, commented: “This work helps solve a fundamental issue in tackling brain diseases by unraveling the unique diversity and nature of cells within the brain. By creating this atlas provides guideposts for others to follow in the study of Parkinson’s.
“Moreover, the work of Drs. Yue, Zhang, and colleagues epitomize the goal of the Parkinson’s Foundation Research Centers—a team coming together to help solve Parkinson’s disease.”
