Dopaminergic neurons (DA) of the substantia nigra pars compacta (SNpc) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA in PD have been limited to genomic or transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined multiomic study examining the protein profile of these neurons is currently available. In this exploratory study, we used laser capture microdissection to extract regions from DA in 10 human SNpc obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nanoliquid chromatography–mass spectrometry, respectively, and the differential expression between PD and control group was assessed. Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This multiomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. This is the first exploratory study analyzing both gene and protein expression of laser-dissected neuronal parts from SNpc in PD. Data are available via ProteomeXchange with identifier PXD024748 and via GEO with identifier GSE 169755.

黑质致密部(SN pc )的多巴胺能神经元 (DA)在帕金森病 (PD) 中选择性地逐渐退化。到目前为止，PD 中 DA 的分子分析仅限于基因组或转录组学方法，而据我们所知，目前还没有蛋白质组学或联合多组学研究检查这些神经元的蛋白质谱。在这项探索性研究中，我们使用激光捕获显微切割从 10 个人 SN pc中的 DA 中提取区域在 PD 患者和对照受试者的尸检中获得。分别通过RNA测序和纳米液相色谱-质谱法鉴定提取的RNA和蛋白质，并评估PD和对照组之间的差异表达。定性分析证实，显微切割协议保留了我们样品的完整性，并提供了对特定分子途径的访问。这种多组学分析突出了 52 种基因和 33 种蛋白质的差异表达，包括已知在 PD 中失调的目标分子，例如LRP2、PNMT、CXCR4、MAOA和CBLN1基因或醛脱氢酶1蛋白。另一方面，尽管两种分析都使用了相同的样本，但 RNA 和蛋白质表达之间的相关性很低，例如编码胱抑素 C 蛋白的CST3基因。这是第一项分析PD 中SN pc的激光解剖神经元部分的基因和蛋白质表达的探索性研究。数据可通过标识符为 PXD024748 的 ProteomeXchange 和标识符为 GSE 169755 的 GEO 获得。