Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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

Ching-Chi Chiu, Tu-Hsueh Yeh, Szu-Chia Lai, Yi-Hsin Weng, Yin-Cheng Huang, Yi-Chuan Cheng, Rou-Shayn Chen, Ying-Zu Huang, June Hung, Chiung-Chu Chen, Wey-Yil Lin, Hsiu-Chen Chang, Yu-Jie Chen, Chao-Lang Chen, Hsin-Yi Chen, Yan-Wei Lin, Yah-Huei Wu-Chou, Hung-Li Wang and Chin-Song Lu _

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Oncotarget. 2016; 7:54215-54227. https://doi.org/10.18632/oncotarget.11090

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Abstract

Ching-Chi Chiu1,4,9,*, Tu-Hsueh Yeh1,2,4,5,*, Szu-Chia Lai1,2,4,5, Yi-Hsin Weng1,2,4,5, Yin-Cheng Huang5,7, Yi-Chuan Cheng5,6, Rou-Shayn Chen1,2,5, Ying-Zu Huang1,2,4,5,8, June Hung1,2,5, Chiung-Chu Chen1,2,5, Wey-Yil Lin1,2,5, Hsiu-Chen Chang1,2,4, Yu-Jie Chen1, Chao-Lang Chen1, Hsin-Yi Chen1, Yan-Wei Lin1, Yah-Huei Wu-Chou1, Hung-Li Wang1,2,3,4 and Chin-Song Lu1,2,4,5

1 Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

2 Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

3 Department of Physiology and Pharmacology, Chang Gung University School of Medicine, Taoyuan, Taiwan

4 Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan

5 College of Medicine, Chang Gung University, Taoyuan, Taiwan

6 Graduate Institute of Biomedical Sciences, Chang Gung University School of Medicine, Taoyuan, Taiwan

7 Department of Neurosurgery, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

8 Institute of Cognitive Neuroscience, National Central University, Taoyuan,Taiwan

9 Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan

* These authors have contributed equally to this work

Correspondence to:

Hung-Li Wang, email:

Chin-Song Lu, email:

Keywords: Parkinson’s disease, Rab35, α-synuclein, biomarker, proteomics, Gerotarget

Received: January 13, 2016 Accepted: June 29, 2016 Published: August 05, 2016

Abstract

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 α-synuclein in dopaminergic SH-SY5Y cells. Co-expression of Rab35 with wild-type or A53T α-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.


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