Faculty Opinions recommendation of Therapeutic targets for cerebral ischemia based on the signaling pathways of the glun2b C terminus.

2015 ◽  
Author(s):  
Mishiya Matsumoto
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathways ◽  
Therapeutic Targets ◽  
C Terminus

scholarly journals Therapeutic Targets for Cerebral Ischemia Based on the Signaling Pathways of the GluN2B C Terminus

Stroke ◽  
2015 ◽  
Vol 46 (8) ◽  
pp. 2347-2353 ◽  
Author(s):  
Yongjun Sun ◽  
Linan Zhang ◽  
You Chen ◽  
Liying Zhan ◽  
Zibin Gao
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathways ◽  
Therapeutic Targets ◽  
C Terminus

Unraveling the action mechanism of Buyang Huanwu Tang (BYHWT) for Cerebral Ischemia by Systematic Pharmacological Methodology

2020 ◽  
Vol 23 ◽  
Author(s):  
Shi-tang Ma ◽  
Ning Zhang ◽  
Ge Hong ◽  
Cheng-tao Feng ◽  
Sheng-wei Hong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Virtual Screening ◽  
Signaling Pathways ◽  
Bioactive Compounds ◽  
Enrichment Analysis ◽  
Material Base ◽  
Lead Discovery ◽  
Binding Effect ◽  
Bioactive Ingredients ◽  
Compound Target

Background: Buyang Huanwu Tang (BYHWT) and relevant Traditional Chinese medicine (TCM) has its unique advantages in the treatment of cerebral ischemia. However, its pharmacological mechanism have not been fully explained. Objective: Base on the multi-component, also the entire disease network targets, the present study set out to identify major bioactive ingredients, key disease targets, and pathways of BYHWT against cerebral ischemia disease by systematic pharmacological methodology. Methods: Both the bioactive compounds from the BYHWT and the positive drugs against cerebral ischemia were fully investigated. The binding targets of the positive drugs were then obtained. A virtual screening protocol was then used to highlight the compound-target interaction. And network was constructed to visual the compound-target binding effect after docking analysis. Moreover，the targets enrichment analysis for biological processes and pathways were revealed to further explore the function of bio-targets protein gene and its role in the signal pathway. Results: A total of 382 active ingredients of the BYHWT and 23 candidate disease targets were identified. Virtual screening results indicated that multiple bioactive compounds targeted multiple proteins. Each compounds act on one or more targets. The mechanisms were linked to 20 signaling pathways, and the key mechanism was related to serotonergic synapse, calcium signaling pathway and camp signaling pathways. Conclusion: The present study explored the bioactive ingredients and mechanisms of BYHWT against cerebral ischemia by systematic pharmacological methodology. the novel methodology would provide a reference for the lead discovery of precursors, disease mechanism and material base for TCM.

scholarly journals Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery

2018 ◽  
Vol 134 ◽  
pp. 208-217 ◽  
Author(s):  
Peiying Li ◽  
R. Anne Stetler ◽  
Rehana K. Leak ◽  
Yejie Shi ◽  
Yan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cerebral Ischemia ◽  
Therapeutic Targets ◽  
Stroke Recovery

Inositide-dependent signaling pathways as new therapeutic targets in myelodysplastic syndromes

2015 ◽  
Vol 20 (6) ◽  
pp. 677-687 ◽  
Author(s):  
Sara Mongiorgi ◽  
Carlo Finelli ◽  
Yong Ryoul Yang ◽  
Cristina Clissa ◽  
James A. McCubrey ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Myelodysplastic Syndromes ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Receptor Crosstalk ◽  
Overt Proteinuria

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.

scholarly journals The C Terminus of the Metabotropic Glutamate Receptor Subtypes 2 and 7 Specifies the Receptor Signaling Pathways

2001 ◽  
Vol 276 (49) ◽  
pp. 45800-45805 ◽  
Author(s):  
Julie Perroy ◽  
Gustavo J. Gutierrez ◽  
Vincent Coulon ◽  
Joel Bockaert ◽  
Jean-Pilippe Pin ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Subtypes ◽  
Receptor Signaling ◽  
Metabotropic Glutamate ◽  
C Terminus

scholarly journals Ykt6 membrane-to-cytosol cycling regulates exosomal Wnt secretion

2018 ◽  
Author(s):  
Karen Linnemannstöns ◽  
Pradhipa Karuna M ◽  
Leonie Witte ◽  
Jeanette Clarissa Kittel ◽  
Adi Danieli ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Long Range ◽  
Protein Trafficking ◽  
Secretory Pathway ◽  
Multivesicular Bodies ◽  
Phosphorylation Sites ◽  
Wnt Proteins ◽  
C Terminus

Protein trafficking in the secretory pathway, for example the secretion of Wnt proteins, requires tight regulation. These ligands activate Wnt signaling pathways and are crucially involved in development and disease. Wnt is transported to the plasma membrane by its cargo receptor Evi, where Wnt/Evi complexes are endocytosed and sorted onto exosomes for long-range secretion. However, the trafficking steps within the endosomal compartment are not fully understood. The promiscuous SNARE Ykt6 folds into an auto-inhibiting conformation in the cytosol, but a portion associates with membranes by its farnesylated and palmitoylated C-terminus. Here, we demonstrate that membrane detachment of Ykt6 is essential for exosomal Wnt secretion. We identified conserved phosphorylation sites within the SNARE domain of Ykt6, which block Ykt6 cycling from the membrane to the cytosol. In Drosophila, Ykt6-RNAi mediated block of Wg secretion is rescued by wildtype but not phosphomimicking Ykt6. The latter accumulates at membranes, while wildtype Ykt6 regulates Wnt trafficking between the plasma membrane and multivesicular bodies. Taken together, we show that a regulatory switch in Ykt6 fine-tunes sorting of Wnts in endosomes.

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