scholarly journals Complementary Transcriptomic and Proteomic Analysis in the Substantia Nigra of Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Bao-hua Dong ◽  
Zhao-qing Niu ◽  
Jing-tao Zhang ◽  
Yi-jing Zhou ◽  
Fan-mei Meng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Proteomic Analysis ◽  
Mrna Level ◽  
Mitochondrial Damage ◽  
Vesicle Transport ◽  
Joint Analysis ◽  
Cell Aging ◽  
Sequencing Data ◽  
New Targets

Parkinson’s disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.

scholarly journals Classifying Parkinson’s Disease Patients With Syntactic and Socio-emotional Verbal Measures

2020 ◽  
Vol 12 ◽  
Author(s):  
Sandra Baez ◽  
Eduar Herrera ◽  
Catalina Trujillo ◽  
Juan F. Cardona ◽  
Jesus A. Diazgranados ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Classification Accuracy ◽  
Functional Role ◽  
Affective State ◽  
Joint Analysis ◽  
Long Distance ◽  
Social Emotions ◽  
Role Assignment ◽  
Joint Assessment

Frontostriatal disorders, such as Parkinson’s disease (PD), are characterized by progressive disruption of cortico-subcortical dopaminergic loops involved in diverse higher-order domains, including language. Indeed, syntactic and emotional language tasks have emerged as potential biomarkers of frontostriatal disturbances. However, relevant studies and models have typically considered these linguistic dimensions in isolation, overlooking the potential advantages of targeting multidimensional markers. Here, we examined whether patient classification can be improved through the joint assessment of both dimensions using sentential stimuli. We evaluated 31 early PD patients and 24 healthy controls via two syntactic measures (functional-role assignment, parsing of long-distance dependencies) and a verbal task tapping social emotions (envy, Schadenfreude) and compared their classification accuracy when analyzed in isolation and in combination. Complementarily, we replicated our approach to discriminate between patients on and off medication. Results showed that specific measures of each dimension were selectively impaired in PD. In particular, joint analysis of outcomes in functional-role assignment and Schadenfreude improved the classification accuracy of patients and controls, irrespective of their overall cognitive and affective state. These results suggest that multidimensional linguistic assessments may better capture the complexity and multi-functional impact of frontostriatal disruptions, highlighting their potential contributions in the ongoing quest for sensitive markers of PD.

scholarly journals Characterization of Parkinson’s disease using blood-based biomarkers: A multicohort proteomic analysis

PLoS Medicine ◽  
2019 ◽  
Vol 16 (10) ◽  
pp. e1002931 ◽  
Author(s):  
Marijan Posavi ◽  
Maria Diaz-Ortiz ◽  
Benjamine Liu ◽  
Christine R. Swanson ◽  
R. Tyler Skrinak ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Proteomic Analysis

scholarly journals Bcl-2-associated athanogene 5 (BAG5) regulates Parkin-dependent mitophagy and cell death

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Mitchell L. De Snoo ◽  
Erik L. Friesen ◽  
Yu Tong Zhang ◽  
Rebecca Earnshaw ◽  
Geneviève Dorval ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Family Member ◽  
Mitochondrial Damage ◽  
Interacting Protein ◽  
Dopaminergic Neurodegeneration ◽  
Defective Clearance ◽  
Promote Cell Death

AbstractAs pathogenic Parkin mutations result in the defective clearance of damaged mitochondria, Parkin-dependent mitophagy is thought to be protective against the dopaminergic neurodegeneration observed in Parkinson’s disease. Recent studies, however, have demonstrated that Parkin can promote cell death in the context of severe mitochondrial damage by degrading the pro-survival Bcl-2 family member, Mcl-1. Therefore, Parkin may act as a ‘switch’ that can shift the balance between protective or pro-death pathways depending on the degree of mitochondrial damage. Here, we report that the Parkin interacting protein, Bcl-2-associated athanogene 5 (BAG5), impairs mitophagy by suppressing Parkin recruitment to damaged mitochondria and reducing the movement of damaged mitochondria into the lysosomes. BAG5 also enhanced Parkin-mediated Mcl-1 degradation and cell death following severe mitochondrial insult. These results suggest that BAG5 may regulate the bi-modal activity of Parkin, promoting cell death by suppressing Parkin-dependent mitophagy and enhancing Parkin-mediated Mcl-1 degradation.

scholarly journals Rs2015 Polymorphism in miRNA Target Site of Sirtuin2 Gene Is Associated with the Risk of Parkinson’s Disease in Chinese Han Population

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Xiongjin Chen ◽  
Hui Mai ◽  
Xiaoting Chen ◽  
Yujie Cai ◽  
Qiufei Cheng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Case Control Study ◽  
Mrna Level ◽  
Case Control ◽  
Chinese Han Population ◽  
Chinese Han ◽  
Han Population ◽  
Functional Assays ◽  
Control Study

Accumulating evidence reveals that the sirtuin family is involved in the pathology of Parkinson’s disease (PD). However, the association between the polymorphisms of the sirtuin gene and the risk of PD remains elusive. Here, we investigated the possible association of nine SIRT1 and SIRT2 SNPs with the risk of PD through a clinical case-control study from the Chinese Han population. Our results showed that rs12778366 in the promoter region of SIRT1 and rs2015 in the 3′untranslated region (3′UTR) of the SIRT2 were significantly associated with the risk of PD. Five SNPs related to SIRT1, rs3740051, rs7895833, rs7069102, rs2273773, and rs4746720 and two SNPs related to SIRT2, rs10410544, and rs45592833 did not show an association with PD risk in this study. Moreover, we found that mRNA level of SIRT2 was upregulated, and mRNA level of SIRT1 was downregulated in the peripheral blood of PD patients compared with healthy controls, and we also observed that SNPs rs12778366 and rs2015 influenced the SIRT1 and SIRT2 expression levels, respectively. Further functional assays suggest that rs2015 may affect the expression of SIRT2 by affecting the binding of miR-8061 to the 3′UTR of SIRT2, ultimately contributing to the risk of PD.

Simulation analysis of the pathogenesis of Parkinson’s disease based on multiple factors leading to mitochondrial damage

2018 ◽  
Vol 22 (S2) ◽  
pp. 4821-4828
Author(s):  
Liu Manqing ◽  
Wan Jin ◽  
Jing Chuya ◽  
Wang Yanyan ◽  
Hong Ganji ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Simulation Analysis ◽  
Mitochondrial Damage ◽  
Multiple Factors

Biochemical properties of the kinase PINK1 as sensor protein for mitochondrial damage signalling

2015 ◽  
Vol 43 (2) ◽  
pp. 287-291 ◽  
Author(s):  
Cornelia Rüb ◽  
Nadja Schröder ◽  
Wolfgang Voos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Causative Factor ◽  
Biochemical Properties ◽  
Mitochondrial Damage ◽  
Mitochondrial Functions ◽  
Biochemical Mechanisms ◽  
Autophagic Process ◽  
Phosphatase And Tensin Homologue

Defects of mitochondrial functions have been implicated in many different human diseases, in particular neurodegenerative diseases. The kinase PINK1 [phosphatase and tensin homologue (PTEN)-induced kinase 1] has been identified as a crucial player in a specific damage signalling pathway, eliminating defective mitochondria by an autophagic process. Mutations in PINK1 have been shown to cause familial cases of Parkinson's disease. In this review, we summarize the biochemical mechanisms that underlie the association of PINK1 with mitochondria under normal and pathological conditions. This unconventional mitochondrial localization pathway is discussed in the context of the role of PINK1 as a sensor of mitochondrial damage and a causative factor in Parkinson's disease.

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