scholarly journals The Parkinson’s disease-linked protein TMEM230 is required for Rab8a-mediated secretory vesicle trafficking and retromer trafficking

2017 ◽  
pp. ddw413 ◽  
Author(s):  
Myung Jong Kim ◽  
Han-Xiang Deng ◽  
Yvette C. Wong ◽  
Teepu Siddique ◽  
Dimitri Krainc
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Vesicle Trafficking ◽  
Secretory Vesicle

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

Expression Profiling of Rectal Biopsies Suggests Altered Enteric Neuropathological Traits in Parkinson’s Disease Patients

2020 ◽  
pp. 1-6
Author(s):  
François Cossais ◽  
Eva Schaeffer ◽  
Sebastian Heinzel ◽  
Jessica Zimmermann ◽  
Beate Niesler ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Expression Profiling ◽  
Vesicle Trafficking ◽  
Healthy Controls ◽  
Mrna Profiling ◽  
Mitochondrial Functions ◽  
Rectal Biopsies ◽  
And Mitochondrial Functions

Still little is known about the nature of the gastrointestinal pathological alterations occurring in Parkinson’s disease (PD). Here, we used multiplexed mRNA profiling to measure the expression of a panel of 770 genes related to neuropathological processes in deep submucosal rectal biopsies of PD patients and healthy controls. Altered enteric neuropathological traits based on the expression of 22 genes related to neuroglial and mitochondrial functions, vesicle trafficking and inflammation was observed in 9 out 12 PD patients in comparison to healthy controls. These results provide new evidences that intestinal neuropathological alterations may occur in a large proportion of PD patients.

scholarly journals LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson’s disease and dementia with Lewy bodies

2021 ◽  
Author(s):  
Martyna M. Grochowska ◽  
◽  
Ana Carreras Mascaro ◽  
Valerie Boumeester ◽  
Domenico Natale ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Brain ◽  
Dementia With Lewy Bodies ◽  
Vesicle Trafficking ◽  
Lewy Bodies ◽  
Specific Pattern ◽  
Loss Of Function ◽  
Control Subjects ◽  
Early Endosomes

AbstractLoss-of-function variants in the low-density lipoprotein receptor-related protein 10 (LRP10) gene have been associated with autosomal-dominant Parkinson’s disease (PD), PD dementia, and dementia with Lewy bodies (DLB). Moreover, LRP10 variants have been found in individuals diagnosed with progressive supranuclear palsy and amyotrophic lateral sclerosis. Despite this genetic evidence, little is known about the expression and function of LRP10 protein in the human brain under physiological or pathological conditions. To better understand how LRP10 variants lead to neurodegeneration, we first performed an in-depth characterisation of LRP10 expression in post-mortem brains and human-induced pluripotent stem cell (iPSC)-derived astrocytes and neurons from control subjects. In adult human brain, LRP10 is mainly expressed in astrocytes and neurovasculature but undetectable in neurons. Similarly, LRP10 is highly expressed in iPSC-derived astrocytes but cannot be observed in iPSC-derived neurons. In astrocytes, LRP10 is present at trans-Golgi network, plasma membrane, retromer, and early endosomes. Interestingly, LRP10 also partially co-localises and interacts with sortilin-related receptor 1 (SORL1). Furthermore, although LRP10 expression and localisation in the substantia nigra of most idiopathic PD and DLB patients and LRP10 variant carriers diagnosed with PD or DLB appeared unchanged compared to control subjects, significantly enlarged LRP10-positive vesicles were detected in a patient carrying the LRP10 p.Arg235Cys variant. Last, LRP10 was detected in Lewy bodies (LB) at late maturation stages in brains from idiopathic PD and DLB patients and in LRP10 variant carriers. In conclusion, high LRP10 expression in non-neuronal cells and undetectable levels in neurons of control subjects indicate that LRP10-mediated pathogenicity is initiated via cell non-autonomous mechanisms, potentially involving the interaction of LRP10 with SORL1 in vesicle trafficking pathways. Together with the specific pattern of LRP10 incorporation into mature LBs, these data support an important mechanistic role for disturbed vesicle trafficking and loss of LRP10 function in neurodegenerative diseases.

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

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.

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