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, Chin Song Lu

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)54215-54227
Number of pages13
JournalOncotarget
Volume7
Issue number34
DOIs
Publication statusPublished - 2016
Externally publishedYes

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Parkinson Disease
Biomarkers
Synucleins
Parkinsonian Disorders
Serum
Progressive Supranuclear Palsy
Multiple System Atrophy
Rotenone
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Substantia Nigra
Age of Onset
Neurodegenerative Diseases
Proteomics
Transgenic Mice
Disease Progression
Electrophoresis
Early Diagnosis
Proteins
Differential Diagnosis
Cell Death

Keywords

  • A-synuclein
  • Biomarker
  • Gerotarget
  • Parkinson's disease
  • Proteomics
  • Rab35

ASJC Scopus subject areas

  • Oncology

Cite this

Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease. / Chiu, Ching Chi; Yeh, Tu Hsueh; Lai, Szu Chia; Weng, Yi Hsin; Huang, Yin Cheng; Cheng, Yi Chuan; Chen, Rou Shayn; Huang, Ying Zu; Hung, June; Chen, Chiung Chu; Lin, Wey Yil; Chang, Hsiu Chen; Chen, Yu Jie; Chen, Chao Lang; Chen, Hsin Yi; Lin, Yan Wei; Wu-Chou, Yah Huei; Wang, Hung Li; Lu, Chin Song.

In: Oncotarget, Vol. 7, No. 34, 2016, p. 54215-54227.

Research output: Contribution to journalArticle

Chiu, CC, Yeh, TH, Lai, SC, Weng, YH, Huang, YC, Cheng, YC, Chen, RS, Huang, YZ, Hung, J, Chen, CC, Lin, WY, Chang, HC, Chen, YJ, Chen, CL, Chen, HY, Lin, YW, Wu-Chou, YH, Wang, HL & Lu, CS 2016, 'Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease', Oncotarget, vol. 7, no. 34, pp. 54215-54227. https://doi.org/10.18632/oncotarget.11090
Chiu, Ching Chi ; Yeh, Tu Hsueh ; Lai, Szu Chia ; Weng, Yi Hsin ; Huang, Yin Cheng ; Cheng, Yi Chuan ; Chen, Rou Shayn ; Huang, Ying Zu ; Hung, June ; Chen, Chiung Chu ; Lin, Wey Yil ; Chang, Hsiu Chen ; Chen, Yu Jie ; Chen, Chao Lang ; Chen, Hsin Yi ; Lin, Yan Wei ; Wu-Chou, Yah Huei ; Wang, Hung Li ; Lu, Chin Song. / Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease. In: Oncotarget. 2016 ; Vol. 7, No. 34. pp. 54215-54227.
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AU - Chiu, Ching Chi

AU - Yeh, Tu Hsueh

AU - Lai, Szu Chia

AU - Weng, Yi Hsin

AU - Huang, Yin Cheng

AU - Cheng, Yi Chuan

AU - Chen, Rou Shayn

AU - Huang, Ying Zu

AU - Hung, June

AU - Chen, Chiung Chu

AU - Lin, Wey Yil

AU - Chang, Hsiu Chen

AU - Chen, Yu Jie

AU - Chen, Chao Lang

AU - Chen, Hsin Yi

AU - Lin, Yan Wei

AU - Wu-Chou, Yah Huei

AU - Wang, Hung Li

AU - Lu, Chin Song

PY - 2016

Y1 - 2016

N2 - 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 a-synuclein in dopaminergic SH-SY5Y cells. Co-expression of Rab35 with wild-type or A53T a-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.

AB - 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 a-synuclein in dopaminergic SH-SY5Y cells. Co-expression of Rab35 with wild-type or A53T a-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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KW - Biomarker

KW - Gerotarget

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KW - Proteomics

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