Schillaci Francesca A, Lanza Giuseppe, Salluzzo Maria Grazia, L'Episcopo Francesca, Ferri Raffaele, Salemi Michele
Oasi Research Institute-IRCCS, 94018 Troina, Italy.
Department of Surgery and Medical-Surgical Specialties, University of Catania, 95125 Catania, Italy.
Int J Mol Sci. 2024 Dec 6;25(23):13107. doi: 10.3390/ijms252313107.
More than six million people worldwide are affected by Parkinson's disease (PD), a multifactorial disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several immunohistochemical studies suggest that neuromelanin (NM), found in these neurons, plays a key role in their degeneration. In this study, twelve formalin-fixed, paraffin-embedded (FFPE) brain sections were analyzed, comprising six samples from PD patients and six from healthy controls. Immunohistochemistry (IHC) was conducted to assess the expression of the ETNPPL protein in these samples. ETNPPL was detected in both PD and control samples. Additionally, we examined the expression of ETNPPL mRNA using Quantitative Real-Time PCR (qRT-PCR) in the same sample set. Notably, in control samples, ETNPPL protein was closely associated with the dark NM pigment in the cytoplasm of SNc dopaminergic neurons. In contrast, PD samples showed weak cytoplasmic expression of ETNPPL, with no association with the NM pigment. No nuclear ETNPPL signal was detected in dopaminergic neurons from either PD patients or controls. qRT-PCR results revealed lower ETNPPL mRNA expression in individual PD patients compared to controls. Importantly, we observed a higher concentration of ETNPPL protein at the NM level in the SNc neurons of controls, consistent with mRNA expression patterns. These findings suggest a potential role for ETNPPL in the normal function of dopaminergic neurons and underscore its altered expression in Parkinson's disease.
全球有超过600万人受到帕金森病（PD）的影响，这是一种多因素疾病，其特征是黑质致密部（SNc）中多巴胺能神经元逐渐丧失。多项免疫组织化学研究表明，这些神经元中发现的神经黑色素（NM）在其退化过程中起关键作用。在本研究中，分析了12个福尔马林固定、石蜡包埋（FFPE）的脑切片，其中包括6个帕金森病患者的样本和6个健康对照的样本。进行免疫组织化学（IHC）以评估这些样本中ETNPPL蛋白的表达。在帕金森病患者和对照样本中均检测到ETNPPL。此外，我们使用定量实时PCR（qRT-PCR）在同一组样本中检测了ETNPPL mRNA的表达。值得注意的是，在对照样本中，ETNPPL蛋白与SNc多巴胺能神经元细胞质中的深色NM色素密切相关。相比之下，帕金森病患者样本中ETNPPL的细胞质表达较弱，与NM色素无关联。在帕金森病患者或对照的多巴胺能神经元中均未检测到核ETNPPL信号。qRT-PCR结果显示，与对照相比，帕金森病患者个体中ETNPPL mRNA表达较低。重要的是，我们观察到对照的SNc神经元中NM水平的ETNPPL蛋白浓度较高，这与mRNA表达模式一致。这些发现表明ETNPPL在多巴胺能神经元的正常功能中可能发挥作用，并强调了其在帕金森病中表达的改变。
