Proteomic Analysis of the Cerebrospinal Fluid of Parkinson's Disease Patients Pre- and Post-Deep Brain Stimulation

Wang, Ersong; Yao, Hui-bin; Chen, Yinghui; Gan, Wang; Gao, Wenwei; Sun, Yirui; Guo, Jianqiang; Hu, Jiayin; Jiang, Chengchuan; Hu, Jin

doi:10.1159/000350082

Cited by 858 publications

(14 citation statements)

References 67 publications

(32 reference statements)

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“…Changes at the proteomic level have been described in the serum, SN and cerebrospinal fluid of PD patients and in the striatum of toxin-induced parkinsonian rats ( Licker et al, 2014 ; Lu et al, 2014 ; Wang et al, 2013 ; Xiong et al, 2014 ). Therefore, we focused on the toxin-induced changes of protein composition and the possible protective effect of PACAP in the 6-OHDA model.…”

Section: Resultsmentioning

confidence: 99%

Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration developed in two parkinsonian models

Maász

Zrínyi

Reglődi

et al. 2016

Disease Models &Amp; Mechanisms

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Pituitary adenylate cyclase-activating polypeptide (PACAP) rescues dopaminergic neurons from neurodegeneration and improves motor changes induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently, we investigated the molecular background of the neuroprotective effect of PACAP in dopamine (DA)-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. Behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7 protein concentrations were measured before and after PACAP treatment in both models. Locomotion and feeding activity were decreased in rotenone-treated snails, which corresponded well to findings obtained in 6-OHDA-induced rat experiments. PACAP was able to prevent the behavioural malfunctions caused by the toxins. Monoamine levels decreased in both models and the decreased DA level induced by toxins was attenuated by ∼50% in the PACAP-treated animals. In contrast, PACAP had no effect on the decreased serotonin (5HT) levels. S-COMT metabolic enzyme was also reduced but a protective effect of PACAP was not observed in either of the models. Following toxin treatment, a significant increase in MB-COMT was observed in both models and was restored to normal levels by PACAP. A decrease in PARK7 was also observed in both toxin-induced models; however, PACAP had a beneficial effect only on 6-OHDA-treated animals. The neuroprotective effect of PACAP in different animal models of Parkinson's disease is thus well correlated with neurotransmitter, enzyme and protein levels. The models successfully mimic several, but not all etiological properties of the disease, allowing us to study the mechanisms of neurodegeneration as well as testing new drugs. The rotenone and 6-OHDA rat and snail in vivo parkinsonian models offer an alternative method for investigation of the molecular mechanisms of neuroprotective agents, including PACAP.

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Section: Resultsmentioning

confidence: 99%

Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration developed in two parkinsonian models

Maász

Zrínyi

Reglődi

et al. 2016

Disease Models &Amp; Mechanisms

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“…Treatments with anticoagulants, conditions precluding the safe performance of the lumbar puncture, use of investigational drugs or devices, or significant lab abnormalities were also exclusionary. Those with ablative brain surgery or DBS were excluded based on study findings of altered protein expression in CSF in PD patients post‐DBS implantation …”

Section: Study Design and Rationalementioning

confidence: 99%

“…Those with ablative brain surgery or DBS were excluded based on study findings of altered protein expression in CSF in PD patients post-DBS implantation. 28…”

Section: Pd Exclusion Criteriamentioning

confidence: 99%

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

et al. 2016

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Background Identifying PD-specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, and variability of collection protocols, and focus on de novo, un-medicated patients. Thus, a platform for biomarker discovery and validation in well-characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson’s Disease) is a cross-sectional, multi-center biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort’s clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined “off” states and “on” states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from “off” state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson’s Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD’s broad and heterogeneous spectrum.

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“…Proteomics were employed to further our understanding of PD pathological mechanisms. Recent proteomic profiling studies in PD have investigated protein changes in the cerebrospinal fluid, plasma, and brain tissue of PD patients and in the brain tissue of MPTP- and 6-OHDA-treated animal models[ 26 , 27 ]. Proteomic research in PD patients and animal models has shown that overt motor symptoms provide little help in the identification of preclinical biomarkers and preventive therapies for PD.…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics in A30P*A53T α-synuclein transgenic mice reveals upregulation of Sel1l

et al. 2017

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α-Synuclein is an abundantly expressed neuronal protein that is at the center of focus in understanding a group of neurodegenerative disorders called synucleinopathies, which are characterized by the intracellular presence of aggregated α-synuclein. However, the mechanism of α-synuclein biology in synucleinopathies pathogenesis is not fully understood. In this study, mice overexpressing human A30P*A53T α-synuclein were evaluated by a motor behavior test and count of TH-positive neurons, and then two-dimensional liquid chromatography-tandem mass spectrometry coupled with tandem mass tags (TMTs) labeling was employed to quantitatively identify the differentially expressed proteins of substantia nigra pars compacta (SNpc) tissue samples that were obtained from the α-synuclein transgenic mice and wild type controls. The number of SNpc dopaminergic neurons and the motor behavior were unchanged in A30P*A53T transgenic mice at the age of 6 months. Of the 4,715 proteins identified by proteomic techniques, 271 were differentially expressed, including 249 upregulated and 22 downregulated proteins. These alterations were primarily associated with mitochondrial dysfunction, oxidative stress, ubiquitin-proteasome system impairment, and endoplasmic reticulum (ER) stress. Some obviously changed proteins, which were validated by western blotting and immunofluorescence staining, including Sel1l and Sdhc, may be involved in the α-synuclein pathologies of synucleinopathies. A biological pathway analysis of common related proteins showed that the proteins were linked to a total of 31 KEGG pathways. Our findings suggest that these identified proteins may serve as novel therapeutic targets for synucleinopathies.

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Proteomic Analysis of the Cerebrospinal Fluid of Parkinson's Disease Patients Pre- and Post-Deep Brain Stimulation

Cited by 858 publications

References 67 publications

Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration developed in two parkinsonian models

Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration developed in two parkinsonian models

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

Quantitative proteomics in A30P*A53T α-synuclein transgenic mice reveals upregulation of Sel1l

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