Lysosomal Alterations in Peripheral Blood Mononuclear Cells of Parkinson's Disease Patients
Lysosomal Alterations in Peripheral Blood Mononuclear Cells of Parkinson's Disease Patients
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DOI：
10.1002/mds.26433
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发表时间：
2015-11-01
影响因子：
8.6
通讯作者：
Stefanis, Leonidas
中科院分区：
文献类型：
--
作者：
Papagiannakis, Nikolaos;Xilouri, Maria;Stefanis, Leonidas
背景资料：据报道，PD脑中溶酶体相关膜蛋白2a和热休克同源70蛋白的表达减少，这些蛋白参与分子伴侣介导的自噬和葡萄糖脑苷脂酶。本研究的目的是确定PD患者外周血单核细胞中溶酶体相关膜蛋白2a、热休克同源物70和葡萄糖脑苷脂酶水平/活性的系统性改变。（G209 A/A53 T）或葡萄糖脑苷脂酶突变携带者和年龄/性别匹配的对照。热休克同源70蛋白水平在所有PD组中均降低，而其mRNA水平仅在遗传未确定组中降低。葡萄糖脑苷脂酶蛋白水平下降，只有在遗传PD组，而增加的mRNA水平和活性降低，检测到只有在葡萄糖脑苷脂酶突变group.Conclusions：减少热休克同源-70水平是一个明显的系统性分子伴侣介导的自噬功能障碍的暗示，无论遗传背景。葡萄糖脑苷脂酶活性可以作为筛选工具，以确定葡萄糖脑苷脂酶突变携带者与PD。(C)2015年国际帕金森和运动障碍协会
Background: Reduced expression of lysosomal-associated membrane protein 2a and heatshock-cognate 70 proteins, involved in chaperone-mediated autophagy and of glucocerebrosidase, is reported in PD brains. The aim of this study was to identify systemic alterations in lysosomal-associated membrane protein 2a, heatshock cognate-70, and glucocerebrosidase levels/activity in peripheral blood mononuclear cells from PD patients.Methods: Protein/mRNA levels were assessed in PD patients from genetically undetermined background, alpha-synuclein (G209A/A53T), or glucocerebrosidase mutation carriers and age-/sex-matched controls.Results: Heatshock cognate 70 protein levels were reduced in all PD groups, whereas its mRNA levels were decreased only in the genetically undetermined group. Glucocerebrosidase protein levels were decreased only in the genetic PD groups, whereas increased mRNA levels and decreased activity were detected only in the glucocerebrosidase mutation group.Conclusions: Reduced heatshock cognate-70 levels are suggestive of an apparent systemic chaperone-mediated autophagy dysfunction irrespective of genetic background. Glucocerebrosidase activity may serve as a screening tool to identify glucocerebrosidase mutation carriers with PD. (C) 2015 International Parkinson and Movement Disorder Society