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

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

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 Dysfunction of Synaptic Vesicle Endocytosis in Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Li Zou ◽  
Ye Tian ◽  
Zhentao Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Synaptic Vesicle ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Progressive Disorder ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. It is a chronic and progressive disorder estimated to affect at least 4 million people worldwide. Although the etiology of PD remains unclear, it has been found that the dysfunction of synaptic vesicle endocytosis (SVE) in neural terminal happens before the loss of dopaminergic neurons. Recently, accumulating evidence reveals that the PD-linked synaptic genes, including DNAJC6, SYNJ1, and SH3GL2, significantly contribute to the disruptions of SVE, which is vital for the pathogenesis of PD. In addition, the proteins encoded by other PD-associated genes such as SNCA, LRRK2, PRKN, and DJ-1 also play key roles in the regulation of SVE. Here we present the facts about SVE-related genes and discussed their potential relevance to the pathogenesis of PD.

scholarly journals Lipids: Key Players That Modulate α-Synuclein Toxicity and Neurodegeneration in Parkinson’s Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3301 ◽  
Author(s):  
Akio Mori ◽  
Yuzuru Imai ◽  
Nobutaka Hattori
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Vesicle ◽  
Dopaminergic Neurons ◽  
Vesicle Membranes ◽  
Synaptic Functions ◽  
Aggregation Processes ◽  
Lipid Interaction ◽  
Altered Lipid

Parkinson’s disease (PD) is the second most common neurodegenerative disease; it is characterized by the loss of dopaminergic neurons in the midbrain and the accumulation of neuronal inclusions, mainly consisting of α-synuclein (α-syn) fibrils in the affected regions. The prion-like property of the pathological forms of α-syn transmitted via neuronal circuits has been considered inherent in the nature of PD. Thus, one of the potential targets in terms of PD prevention is the suppression of α-syn conversion from the functional form to pathological forms. Recent studies suggested that α-syn interacts with synaptic vesicle membranes and modulate the synaptic functions. A series of studies suggest that transient interaction of α-syn as multimers with synaptic vesicle membranes composed of phospholipids and other lipids is required for its physiological function, while an α-syn-lipid interaction imbalance is believed to cause α-syn aggregation and the resultant pathological α-syn conversion. Altered lipid metabolisms have also been implicated in the modulation of PD pathogenesis. This review focuses on the current literature reporting the role of lipids, especially phospholipids, and lipid metabolism in α-syn dynamics and aggregation processes.

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