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An attempt to dissect a peripheral marker based on cell pathology in Parkinson's disease
Journal of Neural Transmission ( IF 3.2 ) Pub Date : 2021-06-09 , DOI: 10.1007/s00702-021-02364-6
Francesca Biagioni 1 , Rosangela Ferese 1 , Filippo Sean Giorgi 2 , Nicola Modugno 1 , Enrica Olivola 1 , Paola Lenzi 2 , Stefano Gambardella 1, 3 , Diego Centonze 1, 4 , Stefano Ruggieri 1 , Francesco Fornai 1, 2
Affiliation  

Peripheral markers in Parkinson’s disease (PD) represent a hot issue to provide early diagnosis and assess disease progression. The gold standard marker of PD should feature the same reliability as the pathogenic alteration, which produces the disease itself. PD is foremost a movement disorder produced by a loss of nigrostriatal dopamine innervation, in which striatal dopamine terminals are always markedly reduced in PD patients to an extent, which never overlaps with controls. Similarly, a reliable marker of PD should possess such a non-overlapping feature when compared with controls. In the present study, we provide a novel pathological hallmark, the autophagosome, which in each PD patient was always suppressed compared with each control subject. Autophagosomes were counted as microtubule-associated proteins 1A/1B light chain 3B (LC3)-positive vacuoles at ultrastructural morphometry within peripheral (blood) blood mononuclear cells (PBMC). This also provides the gold standard to assess the autophagy status. Since autophagy may play a role in the pathogenesis of PD, autophagosomes may be a disease marker, while participating in the biology of the disease. Stoichiometric measurement of α-synuclein despite significantly increased in PD patients, overlapped between PD and control patients. Although the study need to be validated in large populations, the number of autophagy vacuoles is neither related with therapy (the amount was similarly suppressed in a few de novo patients), nor the age in PD or controls.



中文翻译:

基于细胞病理学剖析帕金森病外周标志物的尝试

帕金森病 (PD) 中的外周标志物是提供早期诊断和评估疾病进展的热点问题。PD 的金标准标志物应具有与产生疾病本身的致病性改变相同的可靠性。PD 主要是由黑质纹状体多巴胺神经支配丧失产生的运动障碍,其中 PD 患者的纹状体多巴胺末端总是显着减少到一定程度,这与对照组不重叠。同样,与对照相比,PD 的可靠标记应具有这种非重叠特征。在本研究中,我们提供了一种新的病理标志,即自噬体,与每个对照受试者相比,每个 PD 患者的自噬体总是受到抑制。在外周血单核细胞 (PBMC) 内的超微结构形态测量中,自噬体被计为微管相关蛋白 1A/1B 轻链 3B (LC3) 阳性空泡。这也为评估自噬状态提供了金标准。由于自噬可能在 PD 的发病机制中发挥作用,因此自噬体可能是疾病标志物,同时参与疾病的生物学。α-突触核蛋白的化学计量测量尽管在 PD 患者中显着增加,但在 PD 和对照患者之间重叠。尽管该研究需要在大量人群中进行验证,但自噬空泡的数量既与治疗无关(在少数新发患者中也同样受到抑制),也与 PD 或对照组的年龄无关。

更新日期:2021-06-10
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