Gastrointestinal nervous system α-synuclein as a potential biomarker of Parkinson disease.

Gastrointestinal nervous system α-synuclein as a potential biomarker of Parkinson disease.
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胃肠神经系统α-突触核蛋白作为帕金森病的潜在生物标志物

DOI:
10.1097/md.0000000000011337
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发表时间:
2018-07
期刊:
影响因子:
1.6
通讯作者:
Ye Q
Ye Q
中科院分区:
医学4区
文献类型:
--
作者:
Yan F;Chen Y;Li M;Wang Y;Zhang W;Chen X;Ye Q

文献摘要

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路易小体(LB)在帕金森病(PD)中脑多巴胺能(DA)神经元的发育、存活和功能维持中发挥重要作用。α-突触核蛋白(α-synuclein)是路易小体的主要成分,是帕金森病(PD)治疗的潜在靶点。α-synuclein可在胃肠道(GI)神经系统中检测到,但GI神经系统α-synuclein表达改变与PD发病是否存在关联尚不清楚。这个问题的答案为帕金森病的临床前诊断提供了一个有前途的生物标志物。因此,本研究旨在检测帕金森病患者胃肠道神经系统α-突触核蛋白水平。采用免疫组化染色法检测31例PD患者(PD组)和32例非PD或帕金森综合征患者(对照组)胃肠道神经系统α-突触核蛋白的表达水平。采用χ2检验比较PD组与对照组的差异。除了α-突触核蛋白阳性蛋白的分布外,还评估了该蛋白在各组胃内的区域分布。PD患者胃肠道神经组织中α突触核蛋白过表达。PD组阳性17例,阴性14例。对照组阳性结果7例,阴性结果24例。经χ2检验,χ2 = 7.255, P = 0.01。这些阳性病例在胃肠道系统的分布情况,经χ2检验,P = .949。21个胃组织有7个α-突触核蛋白阳性组织,而胃体(4个α-突触核蛋白阳性组织)高于其他区域。α-synuclein在PD患者胃肠道组织中表达异常,但其在胃肠道中的分布无特异性。通过检测α-突触核蛋白包涵体,胃肠道粘膜活检可被视为PD早期诊断探索的潜在机会。
Lewy bodies (LB) play an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons in Parkinson disease (PD). Alpha-synuclein (α-synuclein) is the major component of Lewy bodies and is a potential target for Parkinson's disease (PD) therapies. α-synuclein can be detected in the gastrointestinal (GI) nervous system, but whether there is any association between altered α-synuclein expression in the GI nervous system and the onset of PD is not known. The answer to this question presents the opportunity for a promising biomarker in the pre-clinical diagnosis of PD. As such, this study aimed to measure the α-synuclein level in the GI nervous system of Parkinson's disease patients. The protein levels of α-synuclein in the GI nervous system of 31 PD patients (PD group) and 32 patients without PD or Parkinsonism-plus syndrome (control group) were evaluated via immunohistochemical staining. The χ2 test was performed to evaluate the differences between the PD group and control group. In addition to the distribution of α-synuclein positive protein, regional distribution of the protein in the stomach was also evaluated across groups. Alpha synuclein overexpression was found in the GI nervous tissue of PD patients. The PD group included 17 positive results and 14 negative results. The control group exhibited 7 positive results and 24 negative results. The χ2 test showed that χ2 = 7.255, P = .01. The distribution of these positive cases in the gastrointestinal system, the χ2 test showed that P = .949. The 21 stomach tissues had 7 α-synuclein positive protein tissues, while the body of stomach (4 α-synuclein positive protein) was higher than in other regions. Aberrant expression of α-synuclein was detected in the GI tissues of PD patients, though the distribution of α-synuclein in the gastrointestinal tract had no specificity. Gastrointestinal mucous biopsy could be regarded as a potential opportunity for the early-stage diagnostic exploration of PD, through the detection of α-synuclein inclusions.