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在帕金森病前驱期有患病风险的患者血液中寻找生物标志物。

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson's Disease at the Prodromal Stage.

机构信息

Department of Neurology, Neurosurgery, and Medical Genetic, Pirogov Russian National Research Medical University, Moscow 117997, Russia.

Federal Center for Brain and Neurotechnologies, Moscow 117513, Russia.

出版信息

Int J Mol Sci. 2023 Jan 17;24(3):1842. doi: 10.3390/ijms24031842.

Abstract

Parkinson's disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in the lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD.

摘要

帕金森病(PD)在其发病多年后被诊断出来,此时黑质纹状体多巴胺能系统已经严重退化,负责调节运动功能。这解释了为什么对患者的治疗效果不佳。因此,神经科的最高优先级之一是开发 PD 的早期(临床前)诊断方法。本研究的目的是寻找处于 PD 发病风险中的患者血液中的变化,这些变化被认为是潜在的诊断生物标志物。在 1835 名患者中,有 26 名患者被纳入风险组,20 名患者被纳入对照组。纳入风险组的主要标准是睡眠行为障碍和嗅觉障碍,次要标准是神经和精神障碍。在风险患者和对照组中,通过 27 项指标评估了血浆组成和淋巴细胞中感兴趣基因的表达。我们在血浆中发现的主要变化包括 L-3,4-二羟基苯丙氨酸(L-DOPA)和尿酸的浓度降低,以及某些类型的 microRNA 的表达增加,以及总氧化状态的增加。反过来,在风险患者的淋巴细胞中,观察到多巴胺 D3 受体基因和淋巴细胞激活基因 3 ()的表达增加,以及蛋白去糖基酶 DJ-1 基因 ()的表达降低。我们在风险患者中发现的血液变化被认为是 PD 前驱期诊断生物标志物的候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/779f/9915927/4026d439ea35/ijms-24-01842-g001.jpg

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