Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease

被引：31

作者：

Chiu, Ching-Chi ^{[1
,4
,9
]}

Yeh, Tu-Hsueh ^{[1
,2
,4
,5
]}

Lai, Szu-Chia ^{[1
,2
,4
,5
]}

Weng, Yi-Hsin ^{[1
,2
,4
,5
]}

Huang, Yin-Cheng ^{[5
,7
]}

Cheng, Yi-Chuan ^{[5
,6
]}

Chen, Rou-Shayn ^{[1
,2
,5
]}

Huang, Ying-Zu ^{[1
,2
,4
,5
,8
]}

Hung, June ^{[1
,2
,5
]}

Chen, Chiung-Chu ^{[1
,2
,5
]}

Lin, Wey-Yil ^{[1
,2
,5
]}

Chang, Hsiu-Chen ^{[1
,2
,4
]}

Chen, Yu-Jie ^{[1
]}

Chen, Chao-Lang ^{[1
]}

Chen, Hsin-Yi ^{[1
]}

Lin, Yan-Wei ^{[1
]}

Wu-Chou, Yah-Huei ^{[1
]}

Wang, Hung-Li ^{[1
,2
,3
,4
]}

Lu, Chin-Song ^{[1
,2
,4
,5
]}

机构：

[1] Chang Gung Mem Hosp Linkou, Neurosci Res Ctr, Taoyuan, Taiwan

[2] Chang Gung Mem Hosp Linkou, Div Movement Disorders, Dept Neurol, Taoyuan, Taiwan

[3] Chang Gung Univ, Sch Med, Dept Physiol & Pharmacol, Taoyuan, Taiwan

[4] Chang Gung Univ, Sch Med, Hlth Aging Res Ctr, Taoyuan, Taiwan

[5] Chang Gung Univ, Coll Med, Taoyuan, Taiwan

[6] Chang Gung Univ, Sch Med, Grad Inst Biomed Sci, Taoyuan, Taiwan

[7] Chiayi Chang Gung Mem Hosp, Dept Neurosurg, Chiayi, Taiwan

[8] Natl Cent Univ, Inst Cognit Neurosci, Taoyuan, Taiwan

[9] Chang Gung Univ Sci & Technol, Dept Nursing, Taoyuan, Taiwan

来源：

ONCOTARGET | 2016年 / 7卷 / 34期

关键词：

Parkinson's disease; Rab35; alpha-synuclein; biomarker; proteomics; Gerotarget; PLASMA APOLIPOPROTEIN A1; SN DOPAMINERGIC-NEURONS; ALPHA-SYNUCLEIN; LRRK2; NEURODEGENERATION; DEGENERATION; AGGREGATION; SECRETION; DIAGNOSIS; INTERACTS;

D O I：

10.18632/oncotarget.11090

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Parkinson's disease (PD) is the second common neurodegenerative disease. Identification of biomarkers for early diagnosis and prediction of disease progression is important. The present comparative proteomic study of serum samples using two-dimensional fluorescence differential gel electrophoresis followed by ELISA confirmation demonstrated that protein expression of Rab35 was increased in PD patients compared with matched control subjects and other parkinsonian disorders, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). The serum level of Rab35 was significantly correlated with the age at onset of PD. The median age of onset in patients with higher Rab35 serum level was 5 years younger than those with lower Rab35 serum level. There was a positive correlation between the Rab35 level and disease duration of PD. Moreover, the protein expression of Rab35 was increased in the substantia nigra but not in the striatum of mouse models of PD, including MPTP-treated mice, rotenone-treated mice, (R1441C) LRRK2 or (G2019S) LRRK2 transgenic mice. Furthermore, overexpression of Rab35 increased the aggregation and secretion of mutant A53T alpha-synuclein in dopaminergic SH-SY5Y cells. Co-expression of Rab35 with wild-type or A53T alpha-synuclein in SH-SY5Y cells deteriorated cell death. Our results suggest that Rab35 is potentially useful in the differential diagnosis of parkinsonian disorders and is implicated in the pathogenesis of PD.

引用

页码：54215 / 54227

页数：13

共 43 条

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