The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 2, 2023

Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms IS. In particular, early proinflammatory response resulting from overactivation resident microglia infiltration circulating monocytes macrophages brain after cerebral ischemia leads to secondary injury. Microglia are innate immune cells that constantly monitor microenvironment under normal conditions. Once occurs, activated produce dual effects neurotoxicity neuroprotection, balance two determines fate damaged neurons. The activation defined as classical (M1 type) or alternative (M2 type). M1 type secrete pro-inflammatory cytokines neurotoxic mediators exacerbate neuronal damage, while M2 promote a repairing anti-inflammatory response. Fine regulation M1/M2 microglial minimize damage maximize protection has therapeutic value. This review focuses on interaction between other involved IS phenotypic characteristics, mechanism natural plant components regulating IS, providing novel candidate drugs for drug development.

Language: Английский

---

Molecular Pathophysiological Mechanisms in Huntington’s Disease

Biomedicines, Journal Year: 2022, Volume and Issue: 10(6), P. 1432 - 1432

Published: June 17, 2022

Huntington's disease is an inherited neurodegenerative described 150 years ago by George Huntington. The genetic defect was identified in 1993 to be expanded CAG repeat on exon 1 of the huntingtin gene located chromosome 4. In following almost 30 years, a considerable amount research, using mainly animal models or vitro experiments, has tried unravel complex molecular cascades through which transcription mutant protein leads neuronal loss, especially medium spiny neurons striatum, and excitotoxicity, transcriptional dysregulation, mitochondrial dysfunction, oxidative stress, impaired proteostasis, altered axonal trafficking reduced availability trophic factors crucial contributors. This review discusses pathogenic literature demise. However, due ubiquitous presence huntingtin, astrocytes are also dysfunctional, neuroinflammation may additionally contribute pathology. quest for therapies delay onset reduce rate progression ongoing, but based findings from basic research.

Language: Английский

---

Developing the Cannabinoid Receptor 2 (CB2) pharmacopoeia: past, present, and future

Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 43(9), P. 754 - 771

Published: July 26, 2022

Language: Английский

---

Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(7), P. 6868 - 6884

Published: July 2, 2024

The onset of neurodegenerative diseases involves a complex interplay pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between stress autophagy in disorders, highlighting as pivotal disease pathogenesis. Reactive oxygen species (ROS) play dual roles cellular homeostasis regulation, with disruptions redox signaling contributing to neurodegeneration. activation Nrf2 pathway represents critical antioxidant mechanism, while maintains by degrading altered cell components. interaction among p62/SQSTM1, Nrf2, Keap1 forms regulatory essential for response, whose dysregulation leads aggregate accumulation. Targeting Nrf2-p62/SQSTM1 holds promise therapeutic intervention, mitigating preserving functions. Additionally, this explores potential synergy endocannabinoid system neuroprotection. Further research is needed elucidate involved molecular mechanisms develop effective strategies against

Language: Английский

---

Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ

Neurochemistry International, Journal Year: 2024, Volume and Issue: 177, P. 105769 - 105769

Published: May 16, 2024

Language: Английский

---

The Alteration of Microglial Calcium Homeostasis in Central Nervous System Disorders: A Comprehensive Review

Neuroglia, Journal Year: 2024, Volume and Issue: 5(4), P. 410 - 444

Published: Oct. 21, 2024

Microglia, the unique and motile immune cells of central nervous system (CNS), function as a security guard in maintaining CNS homeostasis, primarily through calcium signaling. The dynamics microglia control important functions such phagocytosis, cytokine release, migration. Calcium dysregulation has been linked to several disorders, like Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS), ischemic stroke (IS). entering channels voltage-gated (VGCCs), store-operated entry (SOCE), transient receptor potential (TRP) is essential for microglial activation pro-inflammatory responses. Under pathological conditions, formation amyloid-β plaques AD, aggregation α-synuclein PD, oxidative stress MS, exacerbates neuroinflammation, mitochondrial dysfunction, neurodegeneration. Therapeutic strategies targeting signaling pathways, using channel blockers antioxidant interventions, show promise alleviating slowing down progression. This review summarizes underlying mechanisms therapeutic benefits restoring balance disorders.

Language: Английский

---

Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1199 - 1199

Published: June 18, 2022

Inflammation and oxidative stress are interlinked interdependent processes involved in many chronic diseases, including neurodegeneration, diabetes, cardiovascular cancer. Therefore, targeting inflammatory pathways may represent a potential therapeutic strategy. Emerging evidence indicates that phytochemicals extracted from edible plants have the to ameliorate disease phenotypes. In this scenario, ß-caryophyllene (BCP), bicyclic sesquiterpene, carnosic acid (CA), an ortho-diphenolic diterpene, were demonstrated exhibit anti-inflammatory, antioxidant activities, as well neuroprotective mitoprotective effects different vitro vivo models. BCP essentially promotes its by acting selective agonist allosteric modulator of cannabinoid type-2 receptor (CB2R). CA is pro-electrophilic compound that, response oxidation, converted electrophilic form. This can interact activate Keap1/Nrf2/ARE transcription pathway, triggering synthesis endogenous “phase 2” enzymes. However, given nature chemical structure, also exhibits direct effects. readily cross BBB accumulate brain regions, giving rise preventing mitochondrial dysfunction inhibiting activated microglia, substantially through activation pro-survival signalling pathways, regulation apoptosis autophagy, molecular mechanisms related quality control. Findings vitro/in experimental models Parkinson’s Alzheimer’s reported beneficial both compounds, suggesting their use treatments be promising strategy management neurodegenerative diseases aimed at maintaining homeostasis ameliorating glia-mediated neuroinflammation.

Language: Английский

---

Identification and validation of oxidative stress and immune-related hub genes in Alzheimer’s disease through bioinformatics analysis

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Jan. 12, 2023

Abstract Alzheimer’s disease (AD) is the leading cause of dementia in aged population. Oxidative stress and neuroinflammation play important roles pathogenesis AD. Investigation hub genes for development potential therapeutic targets candidate biomarkers warranted. The differentially expressed (DEGs) AD were screened GSE48350 dataset. oxidative (DEOSGs) analyzed by intersection DEGs stress-related genes. immune-related DEOSGs identified weighted gene co-expression network analysis (WGCNA) protein–protein interaction (PPI) analysis, respectively. Enrichment was performed Gene Ontology Kyoto Encyclopedia Genes Genomes. diagnostic value assessed receiver operating characteristic validated GSE1297. mRNA expression determined qRT-PCR analysis. Finally, we constructed drug, transcription factors (TFs), microRNA A total 1160 (259 up-regulated 901 down-regulated) GSE48350. Among them 111 Thereafter, significant difference infiltrated immune cells (effector memory CD8 T cell, activated B natural killer CD56 bright plasmacytoid dendritic neutrophil) between control samples. 27 modules obtained through WGCNA turquoise module most relevant module. We 66 intersecting with 15 PPI them, 9 (CCK, CNR1, GAD1, GAP43, NEFL, NPY, PENK, SST, TAC1) good values verified revealed downregulation CCK, PENK upregulation NEFL 76 agents, 152 miRNAs targets, 91 TFs regulatory networks. Our study key associated reaction pathogenesis. findings may help to provide promising

Language: Английский

---

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3160 - 3160

Published: March 9, 2024

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation cognitive function. molecular underpinnings of sleep modulation by its influence on cell activity are discussed, shedding light reciprocal relationships that govern these processes. Emphasis is placed understanding role cells in mediating neuroinflammatory responses their patterns. Additionally, this review examines how interfaces glia-immune signaling to regulate inflammatory cascades within central nervous system. Notably, consequences disrupted neuroinflammation, dysfunction addressed, encompassing neurodegenerative disorders, mood disturbances, decline. Insights into bidirectional function context explored, providing comprehensive perspective potential mechanisms underlying impairments associated disturbances. Furthermore, therapeutic avenues targeting mitigate restore homeostasis, normalize identification novel targets intricate holds promise addressing conditions characterized dysfunction. This work aims examine complexities neural regulation identify intervention.

Language: Английский

---

Potential of CBD Acting on Cannabinoid Receptors CB1 and CB2 in Ischemic Stroke

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6708 - 6708

Published: June 18, 2024

Stroke is one of the leading causes death. It not only affects adult people but also many children. estimated that, every year, 15 million suffer a stroke worldwide. Among them, 5 die, while are left permanently disabled. In this sense, research to find new treatments should be accompanied with therapies combat neuronal death and avoid developing cognitive impairment dementia. Phytocannabinoids among compounds that have been used by mankind for longest period history. Their beneficial effects such as pain regulation or neuroprotection widely known make them possible therapeutic agents high potential. These bind cannabinoid receptors CB

Language: Английский

---