Gene expression of proteins of the vesicle cycle in dopaminergic neurons in modeling of Parkinson’s disease

Mingazov, E. R.; Ugrumov, M. V.

doi:10.1134/s1607672916030133

Cited by 3 publications

(2 citation statements)

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“…Upregulation of endosomal vesicle trafficking is also associated to Parkinson's disease where an increased RAB5 was found in the striatal neurons. 63 These evidences raised the hypothesis that a tight link between protein-compartment-marker and the vulnerability of cell types within selective brain regions exists. 42 …”

Section: Introductionmentioning

confidence: 99%

Critical importance of RAB proteins for synaptic function

Mignogna

D’Adamo

2017

Small GTPases

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Neurons are highly polarized cells that exhibit one of the more complex morphology and function. Neuronal intracellular trafficking plays a key role in dictating the directionality and specificity of vesicle formation, transport and fusion, allowing the transmission of information in sophisticate cellular network. Thus, the integrity of protein trafficking and spatial organization is especially important in neuronal cells. RAB proteins, small monomeric GTPases belonging to the RAS superfamily, spatially and temporally orchestrate specific vesicular trafficking steps.In this review we summarise the known roles of RAB GTPases involved in the maintenance of neuronal vesicular trafficking in the central nervous system. In particular, we discriminate the axonal pre-synaptic trafficking and dendritic post-synaptic trafficking, to better underlie how a correct orchestration of vesicle movement is necessary to maintain neuronal polarity and then, to permit an accurate architecture and functionality of synaptic activity.

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Section: Introductionmentioning

confidence: 99%

Critical importance of RAB proteins for synaptic function

Mignogna

D’Adamo

2017

Small GTPases

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“…Disorders of the synaptic vesicle cycle participate in the pathogenesis of PD and play a critical role in degeneration of dopaminergic neurons. Synaptotagmin-1 (SYT1), a potential target in treating nervous system disorders, regulates neuron exocytosis and the synaptic vesicle cycle ( Mingazov and Ugrumov, 2016 ; Liu and Kaeser, 2019 ). It has been demonstrated that by sponging miR-34-5p, overexpression of SYT1 has a neuroprotective effect in a mouse model of PD ( Shen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Novel diagnostic biomarkers related to immune infiltration in Parkinson’s disease by bioinformatics analysis

Zhang

Zhao

et al. 2023

Front. Neurosci.

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BackgroundParkinson’s disease (PD) is Pengfei Zhang Liwen Zhao Pengfei Zhang Liwen Zhao a common neurological disorder involving a complex relationship with immune infiltration. Therefore, we aimed to explore PD immune infiltration patterns and identify novel immune-related diagnostic biomarkers.Materials and methodsThree substantia nigra expression microarray datasets were integrated with elimination of batch effects. Differentially expressed genes (DEGs) were screened using the “limma” package, and functional enrichment was analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to explore the key module most significantly associated with PD; the intersection of DEGs and the key module in WGCNA were considered common genes (CGs). The CG protein–protein interaction (PPI) network was constructed to identify candidate hub genes by cytoscape. Candidate hub genes were verified by another two datasets. Receiver operating characteristic curve analysis was used to evaluate the hub gene diagnostic ability, with further gene set enrichment analysis (GSEA). The immune infiltration level was evaluated by ssGSEA and CIBERSORT methods. Spearman correlation analysis was used to evaluate the hub genes association with immune cells. Finally, a nomogram model and microRNA-TF-mRNA network were constructed based on immune-related biomarkers.ResultsA total of 263 CGs were identified by the intersection of 319 DEGs and 1539 genes in the key turquoise module. Eleven candidate hub genes were screened by the R package “UpSet.” We verified the candidate hub genes based on two validation sets and identified six (SYT1, NEFM, NEFL, SNAP25, GAP43, and GRIA1) that distinguish the PD group from healthy controls. Both CIBERSORT and ssGSEA revealed a significantly increased proportion of neutrophils in the PD group. Correlation between immune cells and hub genes showed SYT1, NEFM, GAP43, and GRIA1 to be significantly related to immune cells. Moreover, the microRNA-TFs-mRNA network revealed that the microRNA-92a family targets all four immune-related genes in PD pathogenesis. Finally, a nomogram exhibited a reliable capability of predicting PD based on the four immune-related genes (AUC = 0.905).ConclusionBy affecting immune infiltration, SYT1, NEFM, GAP43, and GRIA1, which are regulated by the microRNA-92a family, were identified as diagnostic biomarkers of PD. The correlation of these four genes with neutrophils and the microRNA-92a family in PD needs further investigation.

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