Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: June 15, 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregation in the brain. Recent studies have revealed critical role of microglia AD pathogenesis. This review provides comprehensive summary current understanding microglial involvement AD, focusing on genetic determinants, phenotypic state, phagocytic capacity, neuroinflammatory response, and impact synaptic plasticity neuronal regulation. Furthermore, recent developments drug discovery targeting are reviewed, highlighting potential avenues for therapeutic intervention. emphasizes essential insights into treatments.

Language: Английский

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M2 microglia-derived exosome-loaded electroconductive hydrogel for enhancing neurological recovery after spinal cord injury

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 3, 2024

Abstract Electroconductive hydrogels offer a promising avenue for enhancing the repair efficacy of spinal cord injuries (SCI) by restoring disrupted electrical signals along cord’s conduction pathway. Nonetheless, application composed diverse electroconductive materials has demonstrated limited capacity to mitigate post-SCI inflammatory response. Recent research indicated that transplantation M2 microglia effectively fosters SCI recovery attenuating excessive Exosomes (Exos), small vesicles discharged cells carrying similar biological functions their originating cells, present compelling alternative cellular transplantation. This investigation endeavors exploit microglia-derived exosomes (M2-Exos) successfully isolated and reversibly bonded through hydrogen bonding synergistic promotion synergistically enhance repair. In vitro experiments substantiated significant M2-Exos-laden stimulate growth neural stem axons in dorsal root ganglion modulate microglial polarization. Furthermore, M2-Exos remarkable ability initial reaction within injury site. When combined with hydrogel, worked expedite neuronal axonal regeneration, substantially functional rats afflicted SCI. These findings underscore potential as valuable reparative factor, amplifying foster rehabilitation.

Language: Английский

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The Role of Microglia in Alzheimer’s Disease From the Perspective of Immune Inflammation and Iron Metabolism

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 30, 2022

Alzheimer’s disease (AD), the most common type of senile dementia, includes complex pathogenesis abnormal deposition amyloid beta-protein (Aβ), phosphorylated tau (p-tau) and neuroimmune inflammatory. The neurodegenerative process AD triggers microglial activation, overactivation microglia produces a large number inflammatory factors. Microglia dysfunction can lead to disturbances in iron metabolism enhance iron-induced neuronal degeneration AD, while elevated levels brain areas affect phenotype function. In this manuscript, we firstly discuss role then introduce immune-inflammatory pathology AD. Their homeostasis is emphasized. Recent studies on ferroptosis are also reviewed. It will help readers better understand provides basis for regulation disorders discovery new potential therapeutic targets

Language: Английский

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Synergistic effects of tetramethylpyrazine and astragaloside IV on spinal cord injury via alteration of astrocyte A1/A2 polarization through the Sirt1-NF-κB pathway

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111686 - 111686

Published: March 10, 2024

Language: Английский

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Synergistic Pharmacological Therapy to Modulate Glial Cells in Spinal Cord Injury

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(3)

Published: Nov. 22, 2023

Abstract Current treatments for modulating the glial‐mediated inflammatory response after spinal cord injury (SCI) have limited ability to improve recovery. This is quite likely due lack of a selective therapeutic approach acting on microgliosis and astrocytosis, glia components most involved trauma, while maximizing efficacy minimizing side effects. A new nanogel that can selectively release active compounds in microglial cells astrocytes developed characterized. The degree selectivity subcellular distribution evaluated by applying an innovative super‐resolution microscopy technique, expansion microscopy. Two different administration schemes are then tested SCI mouse model: early phase, loaded with Rolipram, anti‐inflammatory drug, achieves significant improvement animal's motor performance increased recruitment microglia macrophages able localize lesion. Treatment late however, gives opposite results, worse recovery because widespread degeneration. These findings demonstrate nanovector be functional treatment glial component phases SCI. They also open scenario tackling glia‐mediated inflammation neurodegenerative events central nervous system.

Language: Английский

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Activation of the STING pathway induces peripheral sensitization via neuroinflammation in a rat model of bone cancer pain

Inflammation Research, Journal Year: 2022, Volume and Issue: 72(1), P. 117 - 132

Published: Nov. 8, 2022

Neuroinflammation in the peripheral nervous system has been linked to cancer metastasis-induced bone pain. The stimulator of interferon genes (STING), an innate immune sensor for cytosolic DNA, plays important role inflammation and metastasis is reported be a critical regulator nociception. Here, we examined STING primary nociceptive neurons chronic pain determine if it could new target treating (BCP).Walker 256 cells were injected intratibially induce rats. its downstream inflammatory factors dorsal root ganglia (DRG) detected using western blotting immunofluorescent staining. Transmission electron microscopy BCL2-associated X (Bax) expression used detect mitochondrial stress DRG neurons. C-176, specific inhibitor STING, was block activation test behavior.Mechanical hyperalgesia spontaneous observed BCP rats, accompanied by upregulation ipsilateral L4-5 which showed significant mitochondrion stress. STING/TANK-binding kinase 1 (TBK1)/nuclear factor-kappa B (NF-κB) pathway DRGs rats as well increased IL-1β, IL-6, TNF-α expression. C-176 alleviated reduced pathway.We provide evidence that leads neuroinflammation sensitization. Pharmacological blockade may promising novel strategy preventing BCP.

Language: Английский

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Recent advances in the combination of cellular therapy with stem cells and nanoparticles after a spinal cord injury

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: April 26, 2023

Currently, combined therapies could help to reduce long-term sequelae of spinal cord injury (SCI); stem cell therapy at the site in combination with other has shown very promising results that can be transferred clinical field. Nanoparticles (NPs) are versatile technologies applications medical research for treatments SCI since they deliver therapeutic molecules target tissue and may side effects non-targeted therapies. This article's purpose is analyze concisely describe diverse cellular NPs their regenerative effect after SCI.We reviewed literature related combinatory motor impairment following been published by Web Science, Scopus, EBSCO host, PubMed databases. The covers databases from 2001 December 2022.Animal models have plus cells a positive impact on neuroprotection neuroregeneration. Further required better understand benefits level; therefore, it necessary find select most effective capable exacerbating neurorestorative different then try them out patients SCI. On hand, we consider synthetic polymers such as poly [lactic-co-glycolic acid] (PLGA) candidate design first strategy combines reasons selection PLGA important advantages over NPs, being biodegradable, having low toxicity levels, high biocompatibility; In addition, researchers control release time biodegradation kinetics, importantly, used NMs pathologies (12 studies www.clinicaltrials.gov) approved Federal Food, Drug, Cosmetic Act (FDA).The use worthwhile alternative therapy; however, expected data obtained interventions reflect an variability NPs. Therefore, properly define limits this able continue work same line. Consequently, specific molecule type crucial evaluate its application trials.

Language: Английский

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Neuroprotective effects of tetramethylpyrazine on spinal cord injury-Related neuroinflammation mediated by P2X7R/NLRP3 interaction

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 964, P. 176267 - 176267

Published: Dec. 9, 2023

Language: Английский

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The effects of acteoside on locomotor recovery after spinal cord injury – The role of autophagy and apoptosis signaling pathway

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116607 - 116607

Published: April 30, 2024

In the current study, we investigated effects of acteoside as a phenylpropanoid glycoside on interaction with neurons to assesses locomotor recovery after spinal cord injury (SCI) in rats by focusing evaluating factors involved autophagy, apoptosis, inflammation and oxidative stress processes. 49 Spargue-Dawley were prepared divided into seven healthy SCI groups receiving different concentrations acteoside. After 28 days disease induction treatment acteoside, BBB score test was used evaluate activity. Then, preparing cell homogenates, expression levels MAP1LC3A, MAP-2, glial fibrillary acidic protein (GFAP), Nrf2, Keap-1, Caspase 3 (Casp3), Bax, Bcl-2, TNF-a, IL-1B, reactive oxygen species (ROS), malondialdehyde (MDA) measured. Improvement activity observed two weeks beginning experiment continued until fourth week. Both MAP1LC3A MAP-2 significantly up-regulated treated compared untreated rats, GFAP decreased these animals. Pro-apoptotic proteins Bax Casp3 anti-apoptotic Bcl-2 down-regulated up-regulated, respectively, addition, significant downregulation iNOS, TNF-α, IL-1β decrease contents both ROS MDA well increases Nrf2 Keap-1 seen Furthermore, strongly interacted targets binding affinities -8.3 kcal/mol, -8.5 determined molecular docking studies. general, it can be concluded that has protective considered an adjuvant therapy this disease. However, more studies, especially clinical are needed field.

Language: Английский

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Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(2), P. 557 - 573

Published: April 3, 2024

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for difficulty in repairing nervous tissue after spinal cord injury. Microglia astrocytes play key roles injury micro-environment share a close interaction. However, mechanisms involved remain unclear. In this study, we found that injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 MG3), while reactive scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) its receptor Axl significantly down-regulated vitro experiments showed Gas6 had negative effects on polarization microglia, even inhibited cross-regulation between them. We further demonstrated can inhibit by suppressing activation Yes-associated protein signaling pathway. This, turn, nuclear factor-κB/p65 Janus kinase/signal transducer activator transcription pathways. vivo injured cord, thereby promoting repair motor function recovery. Overall, may role treatment It inflammatory pathway astrocytes, attenuate interaction microenvironment, alleviate local reduce cord.

Language: Английский

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