Microglia Phenotypes in Aging and Neurodegenerative Diseases

Cells, Journal Year: 2022, Volume and Issue: 11(13), P. 2091 - 2091

Published: June 30, 2022

Neuroinflammation is a hallmark of many neurodegenerative diseases (NDs) and plays fundamental role in mediating the onset progression disease. Microglia, which function as first-line immune guardians central nervous system (CNS), are drivers neuroinflammation. Numerous human postmortem studies vivo imaging analyses have shown chronically activated microglia patients with various acute chronic neuropathological diseases. While microglial activation common feature NDs, exact pathological states complex often contradictory. However, there consensus that play biphasic conditions, detrimental protective phenotypes, overall response different phenotypes depends on nature duration inflammatory insult, well stage disease development. This review provides comprehensive overview current research responses health, aging, special emphasis heterogeneous phenotypic such hemorrhagic stroke (HS), Alzheimer's (AD), Parkinson's (PD). The primary focus translational preclinical animal models bulk/single-cell transcriptome samples. Additionally, this covers key receptors signaling pathways potential therapeutic targets to regulate during aging NDs. age-, sex-, species-specific differences will be briefly reviewed.

Language: Английский

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Apoptosis in Alzheimer’s disease: insight into the signaling pathways and therapeutic avenues

APOPTOSIS, Journal Year: 2023, Volume and Issue: 28(7-8), P. 943 - 957

Published: April 26, 2023

Language: Английский

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JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Nov. 8, 2023

Abstract The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological pathological processes such inflammation stress. Dysregulation this can lead to severe immunodeficiencies malignancies, its role extends neurotransduction pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological inflammatory disorders, their application has generally been limited diseases with similar pathogenic features. Despite the modest expression of JAK-STAT CNS, it is crucial for functions cortex, hippocampus, cerebellum, making relevant conditions like Parkinson's disease other neuroinflammatory disorders. Furthermore, influence on serotonin receptors phospholipase C implications stress mood This review expands understanding JAK-STAT, moving beyond traditional contexts explore stress-related disorders CNS function. Recent findings, effectiveness Jakinibs chronic rheumatoid arthritis, expand therapeutic applicability. Advances isoform-specific inhibitors, including filgotinib upadacitinib, promise greater specificity fewer off-target effects. Combination therapies, involving monoclonal antibodies, aiming enhance efficacy also give great hope. Overall, bridges gap between basic science clinical application, elucidating complex human health guiding future interventions. Graphical

Language: Английский

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Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Language: Английский

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Molecular Mechanisms Underlying Neuroinflammation Elicited by Occupational Injuries and Toxicants

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2272 - 2272

Published: Jan. 23, 2023

Occupational injuries and toxicant exposures lead to the development of neuroinflammation by activating distinct mechanistic signaling cascades that ultimately culminate in disruption neuronal function leading neurological neurodegenerative disorders. The entry toxicants into brain causes subsequent activation glial cells, a response known as ‘reactive gliosis’. Reactive cells secrete wide variety molecules perturbations thus play crucial role progression regulation central nervous system (CNS) injury. In parallel, roles protein phosphorylation cell eliciting are evolving. However, there is limited understanding molecular underpinnings associated with toxicant- or occupational injury-mediated neuroinflammation, gliosis, outcomes. has biological significance, including promotion inhibition disease mechanisms. Nevertheless, regulatory mechanisms synergism antagonism among intracellular pathways remain elusive. This review highlights research focusing on direct interaction between immune injury-induced gliosis. Specifically, injuries, e.g., trips, slips, falls resulting traumatic injury, toxicants, volatile organic compounds, metals, nanoparticles/nanomaterials diseases highlighted. Further, this recapitulates recent advancement related characterization comprising signaling, culminating neuroinflammation.

Language: Английский

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JAK2/STAT3 as a new potential target to manage neurodegenerative diseases: An interactive review

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 970, P. 176490 - 176490

Published: March 15, 2024

Language: Английский

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Reactive gliosis in traumatic brain injury: a comprehensive review

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Language: Английский

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Essential Oil Constituents as Anti-Inflammatory and Neuroprotective Agents: An Insight through Microglia Modulation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5168 - 5168

Published: May 9, 2024

Microglia are key players in the brain’s innate immune response, contributing to homeostatic and reparative functions but also inflammatory underlying mechanisms of neurodegeneration. Targeting microglia modulating their function may have therapeutic potential for mitigating neuroinflammation The anti-inflammatory properties essential oils suggest that some components be useful regulating microglial microglial-associated neuroinflammation. This study, starting from ethnopharmacological premises benefits aromatic plants, assessed evidence oil modulation microglia, investigating pharmacological mechanisms. Current knowledge phytoconstituents, safety components, neuroprotective effects were reviewed. review encompasses Thymus spp., Artemisia Ziziphora clinopodioides, Valeriana jatamansi, Acorus others as well including 1,8-cineole, β-caryophyllene, β-patchoulene, carvacrol, β-ionone, eugenol, geraniol, menthol, linalool, thymol, α-asarone, α-thujone. Essential target PPAR/PI3K-Akt/MAPK signalling pathways could supplement other approaches modulate inflammation treat neurodegenerative diseases, particularly cases where reactive play a part pathophysiological

Language: Английский

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Contextual AI models for single-cell protein biology

Nature Methods, Journal Year: 2024, Volume and Issue: 21(8), P. 1546 - 1557

Published: July 22, 2024

Understanding protein function and developing molecular therapies require deciphering the cell types in which proteins act as well interactions between proteins. However, modeling across biological contexts remains challenging for existing algorithms. Here we introduce PINNACLE, a geometric deep learning approach that generates context-aware representations. Leveraging multiorgan single-cell atlas, PINNACLE learns on contextualized interaction networks to produce 394,760 representations from 156 type 24 tissues. PINNACLE's embedding space reflects cellular tissue organization, enabling zero-shot retrieval of hierarchy. Pretrained can be adapted downstream tasks: enhancing 3D structure-based resolving immuno-oncological interactions, investigating drugs' effects types. outperforms state-of-the-art models nominating therapeutic targets rheumatoid arthritis inflammatory bowel diseases pinpoints with higher predictive capability than context-free models. ability adjust its outputs basis context it operates paves way large-scale context-specific predictions biology.

Language: Английский

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DeepDrug as an expert guided and AI driven drug repurposing methodology for selecting the lead combination of drugs for Alzheimer’s disease

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 15, 2025

Language: Английский

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