Vascular dementia: A microglia's perspective

Yang, Yi; Zhao, Xinyuan; Zhu, Zi‐Zhong; Zhang, Lihui

doi:10.1016/j.arr.2022.101734

Cited by 34 publications

(22 citation statements)

References 171 publications

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“…Microglia are the major inflammatory cells in the central nervous system, and their mediated neuroinflammation plays an important role in VD. [55] SRC kinase (SRC) plays a key role in triggering microglia activation and is a key factor involved in the development of neuroinflammation. [56] In addition, both pro-inflammatory cytokines and vascular endothelial dysfunction can induce overexpression of vascular cell adhesion molecule 1 (VCAM1).…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Ginkgo biloba L. leaves in the treatment of vascular dementia based on network pharmacology, molecular docking, and molecular dynamics simulation

Tang

Gai

et al. 2023

Medicine

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Background: Ginkgo biloba L. leaves (GBLs) play a substantial role in the treatment of vascular dementia (VD); however, the underlying mechanisms of action are unclear.Objective: This study was conducted to investigate the mechanisms of action of GBLs in the treatment of VD through network pharmacology, molecular docking, and molecular dynamics simulations. Methods:The active ingredients and related targets of GBLs were screened using the traditional Chinese medicine systems pharmacology, Swiss Target Prediction and GeneCards databases, and the VD-related targets were screened using the OMIM, DrugBank, GeneCards, and DisGeNET databases, and the potential targets were identified using a Venn diagram. We used Cytoscape 3.8.0 software and the STRING platform to construct traditional Chinese medicine-active ingredient-potential target and protein-protein interaction networks, respectively. After gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of potential targets using the DAVID platform, the binding affinity between key active ingredients and targets was analyzed by molecular docking, and finally, the top 3 proteins-ligand pairs with the best binding were simulated by molecular dynamics to verify the molecular docking results.Results: A total of 27 active ingredients of GBLs were screened and 274 potential targets involved in the treatment of VD were identified. Quercetin, luteolin, kaempferol, and ginkgolide B were the core ingredients for treatment, and AKT1, TNF, IL6, VEGFA, IL1B, TP53, CASP3, SRC, EGFR, JUN, and EGFR were the main targets of action. The main biological processes involved apoptosis, inflammatory response, cell migration, lipopolysaccharide response, hypoxia response, and aging. PI3K/Akt appeared to be a key signaling pathway for GBLs in the treatment of VD. Molecular docking displayed strong binding affinity between the active ingredients and the targets. Molecular dynamics simulation results further verified the stability of their interactions. Conclusion subsections:This study revealed the potential molecular mechanisms involved in the treatment of VD by GBLs using multi-ingredient, multi-target, and multi-pathway interactions, providing a theoretical basis for the clinical treatment and lead drug development of VD. Abbreviations: BBB = blood-brain barrier, CCH = chronic cerebral hypoperfusion, DAVID = The Database for Annotation, Visualization and Integrated Discovery, GBE = Ginkgo biloba extract, GBLs = Ginkgo biloba L. leaves, GO = gene ontology, KEGG = kyoto encyclopedia of genes and genomes, OMIM = Online Mendelian Inheritance in Man, PDB = Protein Data Bank, PPI = proteinprotein interactional, RMSD = root mean square deviation, RMSF = root mean square fluctuation, ROG = radius of gyration, ROS = reactive oxygen species, STRING = Protein-Protein Interaction Networks Functional Enrichment Analysis, TCM = traditional Chinese medicine, TCMSP = Traditional Chinese Medicine System Pharmacology Database and Analysis Platform, VD = vascular dementia.

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Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Ginkgo biloba L. leaves in the treatment of vascular dementia based on network pharmacology, molecular docking, and molecular dynamics simulation

Tang

Gai

et al. 2023

Medicine

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“…VD is a clinical syndrome of cognitive dysfunction caused by cerebrovascular diseases, such as cerebral ischemia, cerebral hemorrhage, or brain hypoxia-ischemia (Yang et al, 2022). The main symptoms of VD are impairment of memory and executive ability.…”

Section: Acupuncture Via Nlrp3 Inflammasome In the Vdmentioning

confidence: 99%

Research progress on acupuncture treatment in central nervous system diseases based on NLRP3 inflammasome in animal models

et al. 2023

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Central nervous system (CNS) disorders exhibit complex neurophysiological and pathological mechanisms, which seriously affect the quality of life in patients. Acupuncture, widely accepted as complementary and alternative medicine, has been proven to exert significant therapeutic effects on CNS diseases. As a part of the innate immune system, NLRP3 inflammasome contributes to the pathogenesis of CNS diseases via regulating neuroinflammation. To further explore the mechanisms of acupuncture regulating NLRP3 inflammasome in CNS diseases, our study focused on the effects of acupuncture on neuroinflammation and the NLRP3 inflammasome in vascular dementia, Alzheimer’s disease, stroke, depression, and spinal cord injury. This study confirmed that the activation of NLRP3 inflammasome promotes the development of CNS diseases, and inhibiting the activation of NLRP3 inflammasome is a potential key target for the treatment of CNS diseases. In addition, it is concluded that acupuncture alleviates neuroinflammation by inhibiting the activation of the NLRP3 inflammasome pathway, thereby improving the progression of CNS diseases, which provides a theoretical basis for acupuncture to attenuate neuroinflammation and improve CNS diseases.

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“…Microglial cells are the innate immune cells in the central nervous system (CNS) identified as the early inflammatory response cells, which produce chemokines, cytokines, reactive nitrogen species, and reactive oxygen species (ROS) (Zhang et al., 2021). Accumulating evidence emphasizes the participation of microglia in VaD through the mechanisms of its predominant functions such as phagocytosis, secretory property, chemotaxis, and the crosstalk of it with other neurovascular unit cells (Yang et al., 2022). Cerebral hypoperfusion is a principal risk factor for VaD, and during the recovery phase of cerebral ischemia, converting M1 microglia into the M2 phenotype can reduce inflammatory responses and stimulate neurobehavioral property recovery (Luo et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective mechanism of human umbilical cord mesenchymal stem cell‐derived extracellular vesicles improving the phenotype polarization of microglia via the PI3K/AKT/Nrf2 pathway in vascular dementia

Wang

Mao

et al. 2023

Synapse

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Vascular dementia (VaD) is a prevalent cause of dementia after Alzheimer's disease. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-Evs) are critical for VaD treatment. We explored the mechanism of hUCMSC-Evs in VaD. VaD rat model was established by bilateral common carotid artery ligation and hUCMSC-Evs were extracted. VaD rats were injected with Evs through the tail vein. Rat neurological scores, neural behaviors, memory and learning abilities, brain tissue pathological changes, and neurological impairment were evaluated by Zea-Longa method, Morris water maze tests, HE staining, and ELISA (through acetylcholine [ACH] and dopamine [DA] assessment). Microglia M1/M2 polarization was detected by immunofluorescence staining. Pro-/anti-inflammatory factor levels in brain tissue homogenate, oxidative stress-related indicators, and p-PI3K, PI3K, p-AKT, AKT, and Nrf2 protein levels were determined by ELISA, kits, and Western blot. VaD rats were jointly treated with PI3K phosphorylation inhibitor Ly294002 and hUCMSC-Evs. VaD rats manifested increased neurological function injury scores, decreased cognitive function and learning ability, abnormal brain structure, obvious inflammatory infiltration, diminished ACH and DA levels, increased microglial cells and M1-polarized cells, M1/M2 polarization ratio, inflammation, and oxidative stress. hUCMSC-Evs alleviated the neurological damage of VaD rats, inhibited M1 polarization, inflammation, and oxidative stress of microglial cells in brain tissues of VaD rats, and activated the PI3K/AKT/Nrf2 pathway. Ly294002 partially averted the effects of hUCMSC-Evs on microglial polarization, inflammation, and oxidative stress. Briefly, hUCMSC-Evs activated the PI3K/AKT/Nrf2 pathway and inhibited microglial M1 polarization, inflammation, and oxidative stress, thus protecting VaD rat nerve functions.

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Vascular dementia: A microglia's perspective

Cited by 34 publications

References 171 publications

Exploring the mechanism of Ginkgo biloba L. leaves in the treatment of vascular dementia based on network pharmacology, molecular docking, and molecular dynamics simulation

Exploring the mechanism of Ginkgo biloba L. leaves in the treatment of vascular dementia based on network pharmacology, molecular docking, and molecular dynamics simulation

Research progress on acupuncture treatment in central nervous system diseases based on NLRP3 inflammasome in animal models

Neuroprotective mechanism of human umbilical cord mesenchymal stem cell‐derived extracellular vesicles improving the phenotype polarization of microglia via the PI3K/AKT/Nrf2 pathway in vascular dementia

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