Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, USA.
Genetics. 2021 Aug 9;218(4). doi: 10.1093/genetics/iyab081.
Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. To identify genes that are associated with DA neuron loss, we screened through 201 wild-caught populations of Drosophila melanogaster as part of the Drosophila Genetic Reference Panel. Here, we identify the top-associated genes containing single-nucleotide polymorphisms that render DA neurons vulnerable. These genes were further analyzed by using mutant analysis and tissue-specific knockdown for functional validation. We found that this loss of DA neurons caused progressive locomotor dysfunction in mutants and gene knockdown analysis. The identification of genes associated with the progressive loss of DA neurons should help to uncover factors that render these neurons vulnerable in PD, and possibly develop strategies to make these neurons more resilient.
帕金森病（PD）的主要特征是大脑中多巴胺能（DA）神经元的丧失。然而，人们对为什么 DA 神经元容易受到 PD 的影响知之甚少。为了确定与 DA 神经元丧失相关的基因，我们作为 Drosophila Genetic Reference Panel 的一部分，对 201 个野生果蝇群体进行了筛选。在这里，我们确定了与含有使 DA 神经元易受伤害的单核苷酸多态性的基因相关的顶级关联基因。这些基因进一步通过突变分析和组织特异性敲低进行功能验证。我们发现，这些 DA 神经元的丧失导致突变体的运动功能障碍逐渐恶化，基因敲低分析也是如此。与 DA 神经元进行性丧失相关的基因的鉴定应该有助于揭示使这些神经元在 PD 中易受伤害的因素，并可能制定使这些神经元更具弹性的策略。
