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.

Highlights

  • Parkinson’s disease (PD) is the second common age-related neurodegenerative disease with a prevalence of approximately 1-2% in people over 60 years of age [1]

  • To validate the differential expression of Ras-related protein 35 (Rab35) protein in serum samples, 213 PD patients, 46 progressive supranuclear palsy (PSP) patients, 80 multiple system atrophy (MSA) patients, and 177 healthy control subjects were included for quantitative enzyme linked immunosorbent assay (ELISA) analysis

  • The ANOVA analysis (F=15.18, p < 0.0001) followed by post-hoc multiple comparison using Tukey method showed that the level of Rab35 was significantly higher in serum samples of PD patients compared with control subjects (1.86-fold change, p < 0.0001), PSP group (1.84-fold change, p < 0.01) and MSA group (2.25-fold change, p < 0.0001)

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Summary

Introduction

Parkinson’s disease (PD) is the second common age-related neurodegenerative disease with a prevalence of approximately 1-2% in people over 60 years of age [1]. The clinical presentations are linked to the progressive degeneration of neuromelanin containing dopaminergic neurons in the pars compacta of the www.impactjournals.com/oncotarget Spot no.a. GI Accession Mascot no.b Scorec.

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