Multi-Modal Analysis of Gene Expression from Postmortem Brains and Blood Identifies Synaptic Vesicle Trafficking Genes to Be Associated with Parkinson's Disease

2020 ◽  
Author(s):  
Xiaoya Gao ◽  
Zifeng Huang ◽  
Chaohao Guan ◽  
Cailing Feng ◽  
Ruidong Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Modal Analysis ◽  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Postmortem Brains

Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson’s disease

2020 ◽  
Author(s):  
Xiaoya Gao ◽  
Zifeng Huang ◽  
Cailing Feng ◽  
Chaohao Guan ◽  
Ruidong Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Vesicle ◽  
Multinomial Logistic Regression ◽  
Vesicle Trafficking ◽  
Susceptibility Gene ◽  
Blood Levels ◽  
Ppi Networks ◽  
Postmortem Brains

Abstract Objective We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson’s disease (PD) patients and healthy controls (HC). Methods We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein–protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson’s Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. Results We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. Conclusions This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.

scholarly journals Parkinson's Disease-Associated LRRK2 Hyperactive Kinase Mutant Disrupts Synaptic Vesicle Trafficking in Ventral Midbrain Neurons

2017 ◽  
Vol 37 (47) ◽  
pp. 11366-11376 ◽  
Author(s):  
Ping-Yue Pan ◽  
Xianting Li ◽  
Jing Wang ◽  
James Powell ◽  
Qian Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Ventral Midbrain ◽  
Midbrain Neurons

Synaptic vesicle trafficking and Parkinson's disease

2011 ◽  
Vol 72 (1) ◽  
pp. 134-144 ◽  
Author(s):  
Giovanni Esposito ◽  
Fernandes Ana Clara ◽  
Patrik Verstreken
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Vesicle ◽  
Vesicle Trafficking

The Effect of Dopamine on Gene Expression of Alpha-synuclein and Transcription Factors GATA-1, GATA-2, and ZSCAN21 in Parkinson’s Disease

2018 ◽  
Vol 12 (5) ◽  
pp. 410-418
Author(s):  
A. K. Emelyanov ◽  
A. O. Lavrinova ◽  
E. M. Litusova ◽  
N. A. Knyazev ◽  
D. G. Kulabukhova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Alpha Synuclein

Gene expression of the nicotinic acetylcholine receptor α4 subunit in the frontal cortex in Parkinson's disease patients

1995 ◽  
Vol 187 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Hannsjörg Schröder ◽  
Robert A.I. de Vos ◽  
Ernst N.H. Jansen ◽  
Christina Birtsch ◽  
Andrea Wevers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Frontal Cortex ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine

scholarly journals The universal non-neuronal nature of Parkinson's disease: A theory

2015 ◽  
Author(s):  
André Valente ◽  
Altynay Adilbayeva ◽  
Tursonjan Tokay ◽  
Albert Rizvanov
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Late Onset ◽  
Clinical Signs ◽  
Global Gene Expression ◽  
Neuron Death ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche

Various recent developments of relevance to Parkinson's disease (PD) are discussed and integrated into a comprehensive hypothesis on the nature, origin and inter-cellular mode of propagation of late-onset sporadic PD. We propose to define sporadic PD as a characteristic pathological deviation in the global gene expression program of a cell: the PD expression-state, or PD-state for short. Although a universal cell-generic state, the PD-state deviation would be particularly damaging in a neuronal context, ultimately leading to neuron death and the ensuing observed clinical signs. We review why age accumulated damage caused by oxidative stress in mitochondria could be the trigger for a primordial cell to shift to the PD-state. We put forward hematopoietic cells could be the first to acquire the PD-state, at hematopoiesis, from the disruption in reactive oxygen species (ROS) homeostasis that arises with age in the hematopoietic stem-cell niche. We argue why, nonetheless, such a process is unlikely to explain the shift to the PD-state of all the subsequently affected cells in a patient, thus indicating the existence of a distinct mechanism of propagation of the PD-state. We highlight recent findings on the intercellular exchange of mitochondrial DNA and the ability of mitochondrial DNA to modulate the cellular global gene expression state and propose this could form the basis for the intercellular propagation of the PD-state.

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