Steinbach Simone, Molina Mariana, Grinberg Lea T, Aring Luisa, Guntermann Annika, Marcus Katrin, Heinsen Helmut, Paraizo Leite Renata E, May Caroline
Medizinisches Proteom-Center, Center of Protein Diagnostics (ProDi), Ruhr-Universität Bochum, Bochum, Germany.
Physiopathology in Aging Lab/Brazilian Aging Brain Study Group-LIM22, University of São Paulo Medical School, São Paulo, Brazil.
PLoS One. 2024 Jul 31;19(7):e0296730. doi: 10.1371/journal.pone.0296730. eCollection 2024.
A hallmark of Parkinson's disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier. The underlying reasons for this selective neuronal vulnerability are still unknown. The aim of the present study was to gain a better understanding of molecular differences between these two neuronal subpopulations that may explain the selective neuronal vulnerability within the human substantia nigra. For this purpose, the neurons from the ventral as well as dorsal tier of the substantia nigra were specifically isolated out of neuropathologically unremarkable human substantia nigra sections with laser microdissection. Following, their proteome was analyzed by data independent acquisition mass spectrometry. The samples were analysed donor-specifically and not pooled for this purpose. A total of 5,391 proteins were identified in the substantia nigra. Of these, 2,453 proteins could be quantified in 100% of the dorsal tier samples. 1,629 could be quantified in 100% of the ventral tier samples. Nine proteins were differentially regulated with a log2 value ≥0.5 and a Qvalue ≤0.05. Of these 7 were higher abundant in the dorsal tier and 2 higher in the ventral tier. These proteins are associated with the cytoskeleton, neuronal plasticity, or calcium homeostasis. With these findings a deeper understanding can be gained of the selective neuronal vulnerability within the substantia nigra and of protective mechanisms against neurodegeneration in specific neuronal subpopulations.
帕金森病的一个标志是黑质致密部多巴胺能神经元的特异性退化。有趣的是，并非所有这些神经元都受到相同程度的影响。研究表明，位于黑质致密部腹侧的神经元比背侧层的神经元更容易退化。这种选择性神经元易损性的潜在原因仍然未知。本研究的目的是更好地了解这两个神经元亚群之间的分子差异，这些差异可能解释人类黑质内的选择性神经元易损性。为此，通过激光显微切割从神经病理学无异常的人类黑质切片中特异性分离出黑质腹侧和背侧层的神经元。随后，通过数据非依赖采集质谱分析它们的蛋白质组。样本是针对每个供体进行分析的，而不是为此目的进行合并。在黑质中总共鉴定出5391种蛋白质。其中，2453种蛋白质可以在100%的背侧层样本中定量。1629种可以在100%的腹侧层样本中定量。9种蛋白质的差异调节log2值≥0.5且Q值≤0.05。其中7种在背侧层中丰度较高，2种在腹侧层中丰度较高。这些蛋白质与细胞骨架、神经元可塑性或钙稳态有关。通过这些发现，可以更深入地了解黑质内的选择性神经元易损性以及特定神经元亚群中针对神经退行性变的保护机制。
