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

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11 Citations (Scopus)

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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Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Chiu, C. C., Yeh, T. H., Lai, S. C., Weng, Y. H., Huang, Y. C., Cheng, Y. C., Chen, R. S., Huang, Y. Z., Hung, J., Chen, C. C., Lin, W. Y., Chang, H. C., Chen, Y. J., Chen, C. L., Chen, H. Y., Lin, Y. W., Wu-Chou, Y. H., Wang, H. L., & Lu, C. S. (2016). Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease. Oncotarget, 7(34), 54215-54227. https://doi.org/10.18632/oncotarget.11090