Microglia Mediated Neuroinflammation: Focus on PI3K Modulation

Biomolecules, Journal Year: 2020, Volume and Issue: 10(1), P. 137 - 137

Published: Jan. 14, 2020

Immune activation in the central nervous system involves mostly microglia response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory aimed restore homeostasis. However, prolonged, uncontrolled inflammation may result production by of neurotoxic factors that lead amplification disease state and damage. In particular, specific inducers associated with neurodegenerative diseases activate processes number mediators cytokines enhance processes. Phosphoinositide 3-kinases (PI3Ks) constitute family enzymes regulating wide range activity, including signal transduction. Recent studies have focused attention on intracellular role PI3K its contribution This review illustrates discusses recent findings about this signaling pathway modulation neuroinflammatory responses linked neurodegeneration. Finally, we discuss as potential therapeutic approach helpful for developing innovative strategies diseases.

Language: Английский

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Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease

Mediators of Inflammation, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 20

Published: May 31, 2021

The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is response reactive CNS components to altered homeostasis, regardless cause be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, degenerative, involve direct and indirect immune-related neuroinflammation. Brain infiltrates innate adaptive immune cells appear in an infective otherwise noxious agent produce inflammatory mediators. Mediators include local recruited signals. Processes derived from extrinsic intrinsic diseases also elicit response. A deeper understanding health disease necessary find potential therapeutic targets for preventing reducing damage. This review aimed at discussing functions their roles regulating brain cell responses homeostasis maintenance.

Language: Английский

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Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort

The Lancet Infectious Diseases, Journal Year: 2021, Volume and Issue: 21(11), P. 1557 - 1567

Published: June 21, 2021

BackgroundInfections have been hypothesised to increase the risk of dementia. Existing studies included a narrow range infectious diseases, relied on short follow-up periods, and provided little evidence for whether increased is limited specific dementia subtypes or attributable microbes rather than infection burden. We aimed compare Alzheimer's disease other dementias across wide hospital-treated bacterial viral infections in two large cohorts with long periods.MethodsIn this large, multicohort, observational study, analysis was based primary cohort consisting pooled individual-level data from three prospective Finland (the Finnish Public Sector Health Social Support Still Working study) an independent replication UK Biobank. Community-dwelling adults (≥18 years) no at study entry were included. Follow-up until Dec 31, 2012, 2016, public sector Feb 7, 2018, cohort. Through record linkage national hospital inpatient registers, we ascertained exposure 925 diseases (using International Classification Diseases 10th Revision codes) before onset, identified incident records, medication reimbursement entitlements, death certificates. Hazard ratios (HRs) associations each group (index infection) assessed by use Cox proportional hazards models. then repeated after excluding cases that occurred during first 10 years initial hospitalisation due index infection.FindingsFrom March 1, 1986, Jan 2005, 260 490 people cohort, 19, 2006, Oct 2010, 485 708 In 3 947 046 person-years (median 15·4 [IQR 9·8–21·0]), 77 108 participants had least one onset 2768 developed Hospitalisation any associated (adjusted HR [aHR] 1·48 [95% CI 1·37–1·60]) (2·60 [2·38-2·83]). The association remained when analyses restricted new more (aHR 1·22 1·09–1·36] insufficient analysis), comorbidities factors considered. There dose-response between number episodes both (ptrend=0·0007). Although greatest seen central nervous system (CNS) versus 3·01 2·07–4·37]), excess also evident extra-CNS (1·47 [1·36–1·59]). found difference infection-dementia type infection, stronger vascular 2·09 1·59–2·75] aHR 1·20 [1·08–1·33] 3·28 [2·65–4·04] 1·80 [1·53–2·13] cohort).InterpretationSevere requiring treatment are long-term dementia, including disease. This not CNS infections, suggesting systemic effects sufficient affect brain. absence specificity combined relationships burden support hypothesis driven general inflammation microbes.FundingUK Medical Research Council, US National Institute Aging, Wellcome Trust, NordForsk, Academy Finland, Helsinki Life Science.

Language: Английский

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Microbiota’s role in health and diseases

Environmental Science and Pollution Research, Journal Year: 2021, Volume and Issue: 28(28), P. 36967 - 36983

Published: May 27, 2021

Language: Английский

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Neuroinflammation: A Potential Risk for Dementia

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 616 - 616

Published: Jan. 6, 2022

Dementia is a neurodegenerative condition that considered major factor contributing to cognitive decline reduces independent function. Pathophysiological pathways are not well defined for diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in brain toward their pathology. Microglia central nervous system (CNS) principal components brain’s immune defence and can detect harmful or external pathogens. When stimulated, cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, nitrogen species order preserve cell’s microenvironment. These markers include cytokines IL-1, IL-6, TNFα chemokines CCR3 CCL2 CCR5. Microglial may produce prolonged response that, some circumstances, indicated promotion diseases. The present review focused on involvement microglial cell activation throughout conditions link between dementia.

Language: Английский

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The Role of the JAK/STAT Signaling Pathway in the Pathogenesis of Alzheimer’s Disease: New Potential Treatment Target

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(1), P. 864 - 864

Published: Jan. 3, 2023

Alzheimer’s disease is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in brain. However, emerging evidence suggests that neuroinflammation, mediated notably activated neuroglial cells, neutrophils, macrophages, also plays an important role pathogenesis disease. Therefore, understanding interplay between nervous immune systems might be key to prevention or delay progression. One most mechanisms determining gliogenic cell fate Janus kinase/signal transducer activator transcription (JAK/STAT) signaling pathway influenced overactivation microglia astrocytes. The JAK/STAT one critical factors promote neuroinflammation neurodegenerative diseases such as initiating innate immunity, orchestrating adaptive mechanisms, finally, constraining neuroinflammatory response. Since a chronic environment brain hallmark disease, process would allow establishing underlying then estimating prognosis development finding new potential treatment target. In this review, we highlight recent advances neurological with focus on discussing future research directions regarding novel therapeutic approaches predictive biomarkers for

Language: Английский

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Neuroinflammation and Infection: Molecular Mechanisms Associated with Dysfunction of Neurovascular Unit

Frontiers in Cellular and Infection Microbiology, Journal Year: 2017, Volume and Issue: 7

Published: June 19, 2017

Neuroinflammation is a complex inflammatory process in the central nervous system, which sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and microbial infections are counted as stimuli can challenge host immune system trigger development neuroinflammation. homeostatic nature neuroinflammation essential maintain neuroplasticity. regulated by activity neuronal, glial endothelial cells within neurovascular unit, serves "platform" for coordinated action pro- anti-inflammatory mechanisms. Production mediators (cytokines, chemokines, reactive oxygen species) brain resident migrating from peripheral blood, results impairment blood-brain barrier integrity, thereby further affecting course local inflammation. In this review, we analyzed most recent data on inflammation focused major mechanisms unit dysfunction caused infections.

Language: Английский

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Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain

Frontiers in Immunology, Journal Year: 2017, Volume and Issue: 8

Published: Sept. 4, 2017

Abundant clinical, epidemiological, imaging, genetic, molecular and pathophysiological data together indicate that there occur an unusual inflammatory reaction a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years intense study origin mechanics these AD-relevant pathogenic signals are still not well understood. Here we provide evidence intensely pro-inflammatory bacterial lipopolysaccharide (LPS), part complex mixture neurotoxins arising from abundant Gram-negative bacilli human gastrointestinal (GI) tract, AD affected brain neocortex hippocampus. For first time LPS immuno-histochemical appear to aggregate clumps parenchyma control brains, about 75% anti-LPS were clustered around periphery DAPI-stained nuclei. As is secretory-product resident GI-tract, observations suggest (i) major source may originate internally-derived noxious exudates GI-tract microbiome; (ii) due aging, vascular deficits or degenerative neurotoxic molecules 'leak' into systemic circulation, cerebral vasculature on brain; (iii) this internal microbiome-derived play particularly strong role shaping immune contributing neural degeneration, aging CNS. This 'Perspectives' paper will further highlight some very recent developments implicate as important contributor inflammatory-neurodegeneration

Language: Английский

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Role of the peripheral innate immune system in the development of Alzheimer's disease

Experimental Gerontology, Journal Year: 2017, Volume and Issue: 107, P. 59 - 66

Published: Dec. 21, 2017

Language: Английский

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The Roles of Flavonols/Flavonoids in Neurodegeneration and Neuroinflammation

Mini-Reviews in Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 20(15), P. 1475 - 1488

Published: June 27, 2019

The inflammatory process in the human body is a physiological response involving many cellular types and mediators. It results scar formation to separate damaged area from surrounding healthy tissue. Because of increased blood-brain barrier permeability following inflammation, leukocytes infiltrate CNS are also supplemented by proinflammatory However, an acute after cerebral trauma or stroke may result prolonged lesion formation, leading severe neuronal loss. cause serious damage system. lead such way that endangers functional integration system balance. Effects different flavonoid species on ischemia-reperfusion injury cognition function have been shown experimental studies. Flavonoids presented broadly plants diets. They believed various bioactive effects including anti-viral, anti-inflammatory, cardioprotective, anti-diabetic, anti-cancer, anti-aging, etc. Quercetine predominant dietary flavonoid. Main sources tea, onion, apple. demonstrated frequently consumed food like soybean, peanut, mustard, rice, sesame, olive, potatoes, oats contain flavonoids. Catechin its derivates which isolated tea leaves antioxidant activity but low doses, their prooxidant reported. Ipriflavone synthetic increase total calcium bone. In this review, flavonoids neurodegenerative were examined as general.

Language: Английский

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