Levistilide A ameliorates neuroinflammation via inhibiting JAK2/STAT3 signaling for neuroprotection and cognitive improvement in scopolamine-induced Alzheimer’s disease mouse model

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 110783 - 110783

Published: Aug. 22, 2023

Language: Английский

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Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5925 - 5925

Published: March 21, 2023

Macrophages can be characterized as a very multifunctional cell type with spectrum of phenotypes and functions being observed spatially temporally in various disease states. Ample studies have now demonstrated possible causal link between macrophage activation the development autoimmune disorders. How these cells may contributing to adaptive immune response potentially perpetuating progression neurodegenerative diseases neural injuries is not fully understood. Within this review, we hope illustrate role that macrophages microglia play initiators CNS by offering evidence of: (1) types responses processes antigen presentation each disease, (2) receptors involved macrophage/microglial phagocytosis disease-related debris or molecules, and, finally, (3) implications macrophages/microglia on pathogenesis diseases.

Language: Английский

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Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer’s Disease, Parkinson’s Disease, and Autism Spectrum Disorder

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(7), P. 831 - 831

Published: June 25, 2024

Histamine performs dual roles as an immune regulator and a neurotransmitter in the mammalian brain. The histaminergic system plays vital role regulation of wakefulness, cognition, neuroinflammation, neurogenesis that are substantially disrupted various neurodegenerative neurodevelopmental disorders. H3 receptor (H3R) antagonists inverse agonists potentiate endogenous release brain histamine have been shown to enhance cognitive abilities animal models several Microglial activation subsequent neuroinflammation implicated impacting embryonic adult neurogenesis, contributing development Alzheimer's disease (AD), Parkinson's (PD), autism spectrum disorder (ASD). Acknowledging importance microglia both neurodevelopment, well their by histamine, offers intriguing therapeutic target for these inhibition H3Rs has found facilitate shift from proinflammatory M1 state anti-inflammatory M2 state, leading reduction activity microglial cells. Also, pharmacological studies demonstrated H3R showed positive effects reducing biomarkers, suggesting potential simultaneously modulating crucial neurotransmissions signaling cascades such PI3K/AKT/GSK-3β pathway. In this review, we highlight addressing pathology decline disorders, e.g., AD, PD, ASD, with inflammatory component.

Language: Английский

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CX3CL1 Pathway as a Molecular Target for Treatment Strategies in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8230 - 8230

Published: May 4, 2023

Alzheimer's disease (AD) is a scourge for patients, caregivers and healthcare professionals due to the progressive character of lack effective treatments. AD considered proteinopathy, which means that aetiological clinical features have been linked deposition amyloid β (Aβ) hyperphosphorylated tau protein aggregates throughout brain, with Aβ representing classical hallmarks. However, some other putative mechanisms underlying pathogenesis proposed, including inflammation in microglia activation, impaired hippocampus neurogenesis alterations production release neurotrophic factors. Among all, activation chronic brain gained attention, researchers worldwide wondering whether it possible prevent stop, respectively, onset progression by modulating phenotypes. The following key points established so far: (i) parenchyma represents repeated stimulus determining microglia; (ii) priming make these cells lose neuroprotective functions favour damage loss neurons; (iii) quiescent status at baseline prevents priming, meaning more are quiescent, less they become neurotoxic. Many molecules known modulate state microglia, attracting huge interest among scientists as could be used valuable targets treatment. downside coin came early observation do not display phagocytic ability, being unable clear deposits since phagocytosis crucial clearance efficacy. A solution this issue found modulation baseline, help maintain both ability same time. influence C-X3-chemokine Ligand 1 (CX3CL1), also Fractalkine (FKN), one most investigated. FKN its microglial receptor CX3CR1 players interplay between neurons operation neural circuits efficacy persistence immune response against injury. In addition, CX3CL1 regulates synaptic pruning plasticity developmental age adulthood, when strongly impacts adult. has an effect on phosphorylation, well priming. For all above, CX3CL1/CX3CR1 signalling widely studied relation pathogenesis, biochemical pathway hide molecular novel treatment strategies AD. This review summarizes role use potential target

Language: Английский

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Understanding the mechanisms of disease modifying effects of aerobic exercise in people with Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102202 - 102202

Published: Jan. 23, 2024

Language: Английский

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Microglia and Gut Microbiota: A Double-Edged Sword in Alzheimer's Disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102515 - 102515

Published: Sept. 1, 2024

Language: Английский

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Taurine reduces microglia activation in the brain of aged senescence-accelerated mice by increasing the level of TREM2

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 28, 2024

Abstract Alzheimer’s disease (AD), a chronic neurodegenerative disorder, is the leading cause of dementia. Over-activated microglia related to amyloid-beta (Aβ) and phosphorylated tau (phospho-tau) accumulation in AD brain. Taurine an amino acid with multiple physiological functions including anti-inflammatory effects, has been reported be neuroprotective AD. However, role taurine microglia-mediated remains unclear. Here, we examined effects on brains senescence-accelerated mouse prone 8 (SAMP8) mice by comparing those administered 1% water distilled (DW). We observed increased levels transporter (TAUT) taurine-treated compared control mice. Immunohistochemical Western blot analyses revealed that significantly reduced number activated microglia, phospho-tau Aβ deposit hippocampus cortex. Triggering receptors expressed myeloid cells-2 (TREM2) are known protect against pathogenesis. upregulated TREM2 expression In conclusion, present study suggests treatment may upregulate over-activation decreasing Aβ; providing insight into novel preventive strategy

Language: Английский

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Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer’s disease

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 121, P. 56 - 69

Published: July 21, 2024

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by profound memory impairments, synaptic loss, neuroinflammation, and hallmark pathological markers. High-fat diet (HFD) consumption increases the risk of developing AD even after controlling for metabolic syndrome, pointing to role itself in increasing risk. In AD, complement system, an arm immune system which normally tags redundant or damaged synapses pruning, becomes pathologically overactivated leading tagging healthy synapses. While unhealthy link strong, underlying mechanisms are not well understood part due confounding variables associated with long-term HFD can independently influence brain. Therefore, we experimented short-term regimen isolate diet's impact on brain function without causing obesity. This project investigated effect 1) memory, 2) neuroinflammation including complement, 3) pathology markers, 4) 5) vitro microglial phagocytosis 3xTg-AD mouse model. Following either standard chow HFD, non-Tg mice were tested impairments. separate cohort mice, levels hippocampal inflammatory proteins, markers measured. For last set experiments, BV2 was evaluated. Synaptoneurosomes isolated from hippocampus fed incubated equal numbers microglia. The number microglia that phagocytosed synaptoneurosomes tracked over time live-cell imaging assay. Finally, receptor inhibitor (NIF) repeated Behavioral analysis showed had significantly impaired contextual cued fear compared further HFD. increased expression while decreasing marker only altering HFD-fed at higher rate than those chow-fed suggesting altered blocked this dose-dependent manner, demonstrating HFD-mediated increase dependent. study indicates over-activates cascade resulting poorer memory. data point as potential mechanistic culprit therapeutic target HFD's cognitive vulnerability AD.

Language: Английский

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Is Drp1 a link between mitochondrial dysfunction and inflammation in Alzheimer’s disease?

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: May 12, 2023

Recent advances highlight that inflammation is critical to Alzheimer Disease (AD) pathogenesis. Indeed, several diseases characterized by are considered risk factors for AD, such as type 2 diabetes, obesity, hypertension, and traumatic brain injury. Moreover, allelic variations in genes involved the inflammatory cascade AD. AD also mitochondrial dysfunction, which affects energy homeostasis of brain. The role dysfunction has been mostly neuronal cells. However, recent data demonstrating occurs cells, promoting secretion pro-inflammatory cytokines, turn induce neurodegeneration. In this review, we summarize finding supporting hypothesis inflammatory-amyloid describe demonstrate link between altered cascade. We focus summarizing Drp1, fission, showing Drp1 activation leads NLRP3 inflammasome, cascade, aggravates Amyloid beta (Ab) deposition tau-induced neurodegeneration, relevance pathway an early event

Language: Английский

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Nucleic Acids-Based Biomarkers for Alzheimer’s Disease Diagnosis and Novel Molecules to Treat the Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7893 - 7893

Published: July 19, 2024

Alzheimer's disease (AD) represents the most common form of dementia and affects million people worldwide, with a high social burden considerable economic costs. AD diagnosis benefits from well-established panel laboratory tests that allow ruling-in patients, along FDG amyloid PET imaging tools. The main used to identify patients are Aβ40, Aβ42, Aβ42/Aβ40 ratio, phosphorylated Tau 181 (pTau181) total (tTau). Although they measured preferentially in cerebrospinal fluid (CSF), some evidence about possibility for blood-based determination enter clinical practice is growing up. Unfortunately, CSF biomarkers and, even more, ones, present few flaws, twenty years research this field did not overcome these pitfalls. tale worsens when issue treating addressed due lack effective strategies despite many decades attempts by pharmaceutic industries scientists. Amyloid-based drugs failed stop disease, no neuroinflammation-based have been demonstrated work so far. Hence, only symptomatic therapy available, disease-modifying treatment on hand. Such desolate situation fully justifies active search novel be as reliable molecular targets patients. Recently, group molecules has identified follow-up, nuclei acid-based biomarkers. Nucleic composite extracellular consisting DNA RNA alone or combination other molecules, including proteins. This review article reports findings studies carried out during AD, highlights their advantages limitations.

Language: Английский

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