Neuroinflammation in Alzheimer’s Disease: Current Progress in Molecular Signaling and Therapeutics

Inflammation, Journal Year: 2022, Volume and Issue: 46(1), P. 1 - 17

Published: Aug. 20, 2022

Language: Английский

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Alzheimer Disease Pathogenesis: Insights From Molecular and Cellular Biology Studies of Oligomeric Aβ and Tau Species

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: June 21, 2019

Alzheimer disease (AD) represents an oncoming epidemic that without effective treatment promises to exact extraordinary human and financial burdens. Studies of pathogenesis are essential for defining targets discovering disease-modifying treatments. Past studies AD neuropathology provided valuable, albeit limited, insights. Nevertheless, building on these findings, recent have increasingly rich harvest genetic, molecular cellular data creating unprecedented opportunities both understand treat AD. Among the most significant those documenting presence within brain toxic oligomeric species Aβ tau. Existing support view such can propagate spread neural circuits. To place findings in context we first review genetics AD, including Down syndrome. We detail existence while noting unanswered questions concerning their precise structures, means by which they undergo amplification how induce neuronal dysfunction degeneration. conclude offering a speculative synthesis oligomers tau initiate drive pathogenesis. While 100 years after Alzheimer's report there is much still learn about discovery treatments, application new concepts sophisticated tools poised deliver important advances combatting

Language: Английский

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Gut–Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7551 - 7551

Published: Oct. 13, 2020

The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has largest and vulnerable surface with desirable features to observe foods, nutrients, environmental factors, well differentiate commensals, invading pathogens, others. It is well-known a strong connection central nervous system (CNS) in context health disease. A healthy diverse microbes vital for normal brain functions emotional behaviors. In addition, CNS controls most aspects GI physiology. molecular interaction between gut/microbiome complex bidirectional, ensuring maintenance homeostasis proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, metabolites-dependent pathways. Changes bidirectional relationship GIT are linked pathogenesis neurological disorders; therefore, microbiota/gut-and-brain axis emerging widely accepted concept. this review, we summarize recent findings supporting role microbiota immune on development disorders. highlight advances improving diseases by probiotics/prebiotics/synbiotics fecal transplantation via concept gut–brain axis.

Language: Английский

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Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study

Gut, Journal Year: 2020, Volume and Issue: 70(1), P. 85 - 91

Published: June 23, 2020

Increasing evidence supports reciprocal communication between the enteric and central nervous system in disease, termed 'gut-brain axis'. Recent findings suggest a connection IBD development of Parkinson's disease. The role dementia, another insidious neurodegenerative disorder, has not been explored.

Language: Английский

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Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(13), P. 3161 - 3161

Published: June 28, 2019

Neuroinflammation is an inflammatory response in the brain and spinal cord, which can involve activation of microglia astrocytes. It a common feature many central nervous system disorders, including range neurodegenerative disorders. An overlap between activated microglia, pro-inflammatory cytokines translocator protein (TSPO) ligand binding was shown early animal studies neurodegeneration. These findings have been translated clinical studies, where increases TSPO positron emission tomography (PET) signal occur disease-relevant areas across broad spectrum diseases. While this supports use PET as biomarker to monitor trials novel therapeutics, utility current radioligands has hampered by lack high affinity prevalent form polymorphic (A147T) compared wild type TSPO. This review details recent developments exploration ligand-sensitivity A147T that yielded ligands with improved utility. In addition developing non-discriminating ligand, final frontier research requires understanding cellular functional interpretation signal. Recent insights resulting from single cell analysis microglial phenotypes are reviewed.

Language: Английский

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A mechanistic hypothesis for the impairment of synaptic plasticity by soluble Aβ oligomers from Alzheimer’s brain

Journal of Neurochemistry, Journal Year: 2020, Volume and Issue: 154(6), P. 583 - 597

Published: March 17, 2020

It is increasingly accepted that early cognitive impairment in Alzheimer's disease results considerable part from synaptic dysfunction caused by the accumulation of a range oligomeric assemblies amyloid β-protein (Aβ). Most studies have used synthetic Aβ peptides to explore mechanisms memory deficits rodent models, but recent work suggests isolated human (AD) brain tissue are far more potent and disease-relevant. Although reductionist experiments show oligomers impair plasticity neuronal viability, responsible only partly understood. Glutamatergic receptors, GABAergic nicotinic insulin cellular prion protein, inflammatory mediators, diverse signaling pathways all been suggested. Studies using AD brain-derived soluble suggest certain bioactive forms (principally small, diffusible oligomers) can disrupt plasticity, including binding plasma membranes changing excitatory-inhibitory balance, perturbing mGluR, PrP, other surface proteins, down-regulating glutamate transporters, causing spillover, activating extrasynaptic GluN2B-containing NMDA receptors. We synthesize these emerging data into mechanistic hypothesis for failure be modified as new knowledge added specific therapeutics developed.

Language: Английский

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The complexity of Alzheimer’s disease: an evolving puzzle

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(3), P. 1047 - 1081

Published: Jan. 21, 2021

The history of Alzheimer's disease (AD) started in 1907, but we needed to wait until the end century identify components pathological hallmarks and genetic subtypes formulate first pathogenic hypothesis. Thanks biomarkers new technologies, concept AD then rapidly changed from a static view an amnestic dementia presenium biological entity that could be clinically manifested as normal cognition or different types. What is clearly emerging studies heterogeneous each aspect, such amyloid composition, tau distribution, relation between tau, clinical symptoms, background, thus it probably impossible explain with single process. scientific approach suffers chronological mismatches clinical, pathological, technological data, causing difficulty conceiving diagnostic gold standards creating models for drug discovery screening. A recent mathematical computer-based offers opportunity study real life provide point final missing pieces puzzle.

Language: Английский

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Physical Exercise Inhibits Inflammation and Microglial Activation

Cells, Journal Year: 2019, Volume and Issue: 8(7), P. 691 - 691

Published: July 9, 2019

Accumulating evidence indicates that exercise can enhance brain function and attenuate neurodegeneration. Besides improving neuroplasticity by altering the synaptic structure in various regions, also modulates multiple systems are known to regulate neuroinflammation glial activation. Activated microglia several pro-inflammatory cytokines play active roles pathogenesis of neurodegenerative diseases, such as Alzheimer's disease Parkinson's disease. The purpose this review is highlight impacts on microglial Possible mechanisms involved exercise-modulated activation discussed. Undoubtedly, more studies needed order disclose detailed mechanisms, but approach offers therapeutic potential for health millions aging people where pharmacological intervention has failed.

Language: Английский

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Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: March 5, 2022

The implication of gut microbiota in the control brain functions health and disease is a novel, currently emerging concept. Accumulating data suggest that exert its action at least part by modulating neuroinflammation. Given link between neuroinflammatory changes neuronal activity, it plausible may affect indirectly impacting microglia, key player Indeed, increasing evidence suggests interplay microglia synaptic dysfunction involve microbiota, among other factors. In addition to these indirect microglia-dependent actions on has been recently recognized could also activity directly stimulation vagus nerve.

Language: Английский

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Adult Hippocampal Neurogenesis in Aging and Alzheimer's Disease

Stem Cell Reports, Journal Year: 2021, Volume and Issue: 16(4), P. 681 - 693

Published: Feb. 26, 2021

Cognitive deficits associated with Alzheimer's disease (AD) severely impact daily life for the millions of affected individuals. Progressive memory impairment in AD patients is degeneration hippocampus. The dentate gyrus hippocampus, a region critical learning and functions, site adult neurogenesis mammals. Recent evidence humans indicates that hippocampal likely persists throughout life, but declines age strikingly impaired AD. Our understanding how supports healthy adults only beginning to emerge. extent which decreased contributes cognitive decline aging remains poorly understood. However, studies rodent models other neurodegenerative diseases raise possibility targeting may ameliorate dysfunction Here, we review recent progress impacted context

Language: Английский

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