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基于寻找运动前症状和血液变化等生物标志物的帕金森病早期诊断研究进展

[Development of early diagnosis of Parkinson's disease based on the search for biomarkers such as premotor symptoms and changes in blood].

作者信息

Gusev E I, Katunina E A, Martinov M Yu, Blokhin V E, Kalinkin A L, Alesenko A V, Nodel M R, Malykhina E A, Titova N V, Katunin D A, Shupik M A, Gutner U A, Maloshitskaya O A, Sokolov S A, Kucheryanu V G, Pavlova E N, Ugrumov M V

机构信息

Pirogov Russian National Research Medical University, Moscow, Russia.

Federal Center for Brain and Neurotechnologies, Moscow, Russia.

出版信息

Zh Nevrol Psikhiatr Im S S Korsakova. 2020;120(12):7-17. doi: 10.17116/jnevro20201201217.

Abstract

OBJECTIVE

To determine changes in the chemical composition of blood plasma in subjects at risk of Parkinson's disease (PD) at the prodromal stage compared with age control.

MATERIAL AND METHODS

Subjects at risk were selected for the presence of characteristic premotor symptoms, including impairments of sleep, olfaction and constipation.The risk group included 12 people, the control group - 8 people.

RESULTS

Among seven catecholamines and their metabolites detected in the blood, only the concentration of L-dioxiphenylalanine (L-DOPA) changed (decreased) in subjects at risk compared with the control. A decrease in the concentration of L-DOPA is considered as a manifestation (marker) of selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the concentration of seven of the twelve detected sphingomyelins in the blood of the subjects at risk increased. Given that a change in the metabolism of sphingomyelins is associated with processes such as apoptosis, autophagy, and synucleinopathy, an increase in their concentration in the blood of patients at risk is considered as a manifestation of systemic general degeneration of central and peripheral neurons. Finally, in the blood of subjects at risk, we found a trend towards a decrease in the concentration of urates, which are endogenous neuroprotectors.

CONCLUSION

The changes in the level of L-DOPA, sphingmyelins and urates in the blood of subjects at risk may serve as diagnostic markers of PD at the prodromal stage.

摘要

目的

确定帕金森病(PD)前驱期有患病风险的受试者与年龄匹配的对照组相比血浆化学成分的变化。

材料与方法

根据存在包括睡眠、嗅觉和便秘障碍等特征性运动前症状来选择有患病风险的受试者。风险组包括12人,对照组包括8人。

结果

在血液中检测到的七种儿茶酚胺及其代谢产物中,与对照组相比,有患病风险的受试者中只有L - 二羟苯丙氨酸(L - DOPA)的浓度发生了变化(降低)。L - DOPA浓度降低被认为是PD中枢和外周儿茶酚胺能神经元选择性变性的一种表现(标志物)。与L - DOPA相反,有患病风险的受试者血液中检测到的十二种鞘磷脂中的七种浓度升高。鉴于鞘磷脂代谢的变化与细胞凋亡、自噬和突触核蛋白病等过程相关,其在有患病风险的患者血液中的浓度升高被认为是中枢和外周神经元系统性普遍变性的一种表现。最后,在有患病风险的受试者血液中,我们发现内源性神经保护剂尿酸盐的浓度有降低的趋势。

结论

有患病风险的受试者血液中L - DOPA、鞘磷脂和尿酸盐水平的变化可能作为PD前驱期的诊断标志物。

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