title: Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease.
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.
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.|Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors: Ching-Chi
authors: CC
authors: Chiu
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Tu-Hsueh
authors: TH
authors: Yeh
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Szu-Chia
authors: SC
authors: Lai
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Yi-Hsin
authors: YH
authors: Weng
authors: College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Neurosurgery, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors: Yin-Cheng
authors: YC
authors: Huang
authors: College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Biomedical Sciences, Chang Gung University School of Medicine, Taoyuan, Taiwan.
authors: Yi-Chuan
authors: YC
authors: Cheng
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Rou-Shayn
authors: RS
authors: Chen
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Institute of Cognitive Neuroscience, National Central University, Taoyuan,Taiwan.
authors: Ying-Zu
authors: YZ
authors: Huang
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: June
authors: J
authors: Hung
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Chiung-Chu
authors: CC
authors: Chen
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Wey-Yil
authors: WY
authors: Lin
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.
authors: Hsiu-Chen
authors: HC
authors: Chang
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors: Yu-Jie
authors: YJ
authors: Chen
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors: Chao-Lang
authors: CL
authors: Chen
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors: Hsin-Yi
authors: HY
authors: Chen
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors: Yan-Wei
authors: YW
authors: Lin
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors: Yah-Huei
authors: YH
authors: Wu-Chou
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Department of Physiology and Pharmacology, Chang Gung University School of Medicine, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.
authors: Hung-Li
authors: HL
authors: Wang
authors: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Healthy Aging Research Center, Chang Gung University School of Medicine, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Chin-Song
authors: CS
authors: Lu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000175:diagnosis / Q000209:etiology*; D013378:Substantia Nigra / Q000737:chemistry; D051844:alpha-Synuclein / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; C511183:RAB35 protein, human; D020691:rab GTP-Binding Proteins
keywords: Gerotarget; Parkinson’s disease; Rab35; biomarker; proteomics; α-synuclein