Inflammation as a central mechanism in Alzheimer's disease

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2018, Volume and Issue: 4(1), P. 575 - 590

Published: Jan. 1, 2018

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques neurofibrillary tangles. Over last decade, sustained immune response in brain has emerged as third pathology AD. The activation brain's resident macrophages (microglia) other cells been demonstrated to exacerbate both tau may serve link pathogenesis disorder. In following review, we provide an overview inflammation AD detailed coverage number microglia‐related signaling mechanisms have implicated Additional information on microglia cytokines are also reviewed. We review potential connection risk factors for how they be related inflammatory mechanisms.

Language: Английский

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Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Dec. 18, 2018

Microglia represent a specialized population of macrophages-like cells in the central nervous system (CNS) considered immune sentinels that are capable orchestrating potent inflammatory response. also involved synaptic organizatio, trophic neuronal support during development, phagocytosis apoptotic developing brain, myelin turnover, control excitability, phagocytic debris removal as well brain protection and repair. Microglial response is pathology dependent affects to immune, metabolic. In this review, we will shed light on microglial activation depending disease context influence factors such aging, environment or cell-to-cell interaction.

Language: Английский

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NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies

Frontiers in Cellular Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: March 8, 2017

Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense be activated by wide range exogenous endogenous stimuli such microbes, aggregated misfolded proteins, adenosine triphosphate, which results activation caspase-1. Activated caspase-1 subsequently leads to processing interleukin-1β (IL-1β) interleukin-18 (IL-18) pro-inflammatory cytokines mediates rapid cell death. IL-1β IL-18 drive inflammatory responses through diverse downstream signaling pathways, leading neuronal damage. Thus, NLRP3 inflammasome considered key contributor development neuroinflammation. In this review, we briefly discuss structure address involvement several disorders, brain infection, acute injury, neurodegenerative addition, review series promising therapeutic approaches target including anti-IL-1 therapy, small molecule inhibitors other compounds, however, these are still experimental At present, it plausible generate cell-specific conditional knockout mice via Cre investigate role may instrumental novel pharmacologic investigations for neuroinflammation-associated

Language: Английский

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An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: March 21, 2018

Inflammation is a complex biological response fundamental to how the body deals with injury and infection eliminate initial cause of cell effect repair. Unlike normally beneficial acute inflammatory response, chronic inflammation can lead tissue damage ultimately its destruction, often results from an inappropriate immune response. in nervous system ('neuroinflammation'), especially when prolonged, be particularly injurious. While per se may not disease, it contributes importantly disease pathogenesis across both peripheral (neuropathic pain, fibromyalgia) central (e.g. Alzheimer Parkinson multiple sclerosis, motor neuron disease. ischemia traumatic brain injury, depression, autism spectrum disorder) systems. The existence extensive lines communication between represents principle underlying neuroinflammation. Immune cell-derived molecules are critical for regulation host responses inflammation. Although these mediators originate various non-neuronal cells, important sources above neuropathologies appear microglia mast together astrocytes possibly also oligodendrocytes. Understanding neuroinflammation requires appreciation that – interactions, glia cells themselves, integral part process. Within this context occupies key niche orchestrating process, initiation prolongation. This review will describe current state knowledge concerning biology neuroinflammation, emphasizing cell-glia glia-glia then conclude consideration cell’s endogenous mechanisms might leveraged provide therapeutic strategy target

Language: Английский

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Tryptophan Metabolism and Gut-Brain Homeostasis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(6), P. 2973 - 2973

Published: March 15, 2021

Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player the microbiota-gut-brain axis. It only precursor neurotransmitter serotonin, which vital processing of emotional regulation, hunger, sleep, and pain, well colonic motility secretory activity gut. catabolites from kynurenine degradation pathway also modulate neural are active systemic inflammatory cascade. Additionally, tryptophan its metabolites support development central enteric nervous systems. Accordingly, dysregulation plays role pathogenesis many neurologic psychiatric disorders. Gut microbes influence metabolism directly indirectly, with corresponding changes behavior cognition. The gut microbiome thus garnered much attention therapeutic target both disorders where play prominent role. In this review, we will touch upon some these features their involvement health disease.

Language: Английский

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Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Sept. 10, 2020

Abstract Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model TBI that mild forms trauma severe deficits meningeal lymphatic drainage begin within hours last out to at least one month post-injury. To investigate mechanism underlying impaired function TBI, examined how increased intracranial pressure (ICP) influences the lymphatics. We ICP can contribute dysfunction. Moreover, show pre-existing dysfunction before leads neuroinflammation negative cognitive outcomes. Finally, report rejuvenation aged mice ameliorate TBI-induced gliosis. These findings provide insights into both causes consequences suggest therapeutics targeting system may offer strategies treat TBI.

Language: Английский

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Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders

Biochemical Pharmacology, Journal Year: 2015, Volume and Issue: 103, P. 1 - 16

Published: Nov. 8, 2015

Language: Английский

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The role of astrocytes in oxidative stress of central nervous system: A mixed blessing

Cell Proliferation, Journal Year: 2020, Volume and Issue: 53(3)

Published: Feb. 8, 2020

Abstract Central nervous system (CNS) maintains a high level of metabolism, which leads to the generation large amounts free radicals, and it is also one most vulnerable organs oxidative stress. Emerging evidences have shown that, as key homeostatic cells in CNS, astrocytes are deeply involved multiple aspects CNS function including stress regulation. Besides, redox can turn affect morphology function. The complex roles indicate that their correct performance crucial for normal functioning its dysfunction may result occurrence progression various neurological disorders. To date, influence rarely reviewed. Therefore, this review we sum up regulation corresponding mechanisms under both different pathological conditions.

Language: Английский

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Neuroinflammation in animal models of traumatic brain injury

Journal of Neuroscience Methods, Journal Year: 2016, Volume and Issue: 272, P. 38 - 49

Published: July 3, 2016

Language: Английский

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Mechanisms of Blood–Brain Barrier Dysfunction in Traumatic Brain Injury

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(9), P. 3344 - 3344

Published: May 8, 2020

Traumatic brain injuries (TBIs) account for the majority of injury-related deaths in United States with roughly two million TBIs occurring annually. Due to spectrum severity and heterogeneity TBIs, investigation into secondary injury is necessary order formulate an effective treatment. A mechanical consequence trauma involves dysregulation blood–brain barrier (BBB) which contributes exposure peripheral components parenchyma. Recent studies have shed light on mechanisms BBB breakdown TBI including novel intracellular signaling cell–cell interactions within niche. The current review provides overview BBB, detection methods disruption, cellular molecular implicated regulating its stability following TBI.

Language: Английский

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