Signaling inflammation across the gut-brain axis

Science, Journal Year: 2021, Volume and Issue: 374(6571), P. 1087 - 1092

Published: Nov. 25, 2021

The brain and gastrointestinal tract are critical sensory organs responsible for detecting, relaying, integrating, responding to signals derived from the internal external environment. At interface of this function, immune cells in intestines consistently survey environmental factors, eliciting responses that inform on physiological state body. Recent research reveals cross-talk along gut-brain axis regulates inflammatory nociception, responses, homeostasis. Here, we discuss molecular cellular mechanisms involved signaling inflammation across axis. We further highlight interactions between gut inflammation-associated diseases.

Language: Английский

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Function and therapeutic value of astrocytes in neurological diseases

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(5), P. 339 - 358

Published: Feb. 16, 2022

Language: Английский

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Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 251 - 277

Published: Feb. 9, 2021

The immune system of the central nervous (CNS) consists primarily innate cells. These are highly specialized macrophages found either in parenchyma, called microglia, or at CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were thought phagocytes, their function extends well beyond simple removal cell debris during development diseases. Brain-resident cells to be plastic, long-lived, host an outstanding number risk genes for multiple pathologies. As a result, now considered most suitable targets modulating Additionally, recent single-cell technologies enhanced our molecular understanding origins, fates, interactomes, functional statesduring health perturbation. Here, we review current state challenges myeloid biology treatment options related

Language: Английский

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(7), P. 395 - 409

Published: June 12, 2023

Language: Английский

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Barcoded viral tracing of single-cell interactions in central nervous system inflammation

Science, Journal Year: 2021, Volume and Issue: 372(6540)

Published: April 22, 2021

Single-cell analysis of CNS interactions Despite their importance in the physiology and pathology central nervous system (CNS), few methods are available for unbiased, systematic investigation cell-to-cell at single-cell resolution. Clark et al. developed RABID-seq, a method that combines barcoded viral tracing with RNA sequencing (see Perspective by Silvin Ginhoux). RABID-seq identified axon guidance molecules Sema4D-PlexinB2 EphrinB3-EphB3 as mediators microglia-astrocyte promote experimental autoimmune encephalomyelitis and, potentially, multiple sclerosis. These studies also candidate therapeutic modulation Science , this issue p. eabf1230 ; see 342

Language: Английский

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Solving neurodegeneration: common mechanisms and strategies for new treatments

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

Published: March 21, 2022

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology site disease pathology. To address these and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus the Melza M. Frank Theodore Barr Foundation collaborated to bring together key opinion leaders experts field for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style focused uncovering mechanistic roots promising new catalyzed by goal finding treatments glaucoma, world's leading cause irreversible blindness interest three hosting foundations. Glaucoma, which causes vision loss through degeneration optic nerve, likely shares early cellular molecular events with other diseases central nervous system. Here we major areas overlap between system: neuroinflammation, bioenergetics metabolism, genetic contributions, neurovascular interactions. We summarize important discussion points emphasis research that are most innovative treatment neurodegeneration yet require further development. The is highlighted provides unique opportunities collaboration will lead efforts preventing ultimately loss.

Language: Английский

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Transforming the understanding of brain immunity

Science, Journal Year: 2023, Volume and Issue: 380(6640)

Published: April 6, 2023

Contemporary studies have completely changed the view of brain immunity from envisioning as isolated and inaccessible to peripheral immune cells an organ in close physical functional communication with system for its maintenance, function, repair. Circulating reside special niches brain's borders, choroid plexus, meninges, perivascular spaces, which they patrol sense a remote manner. These niches, together meningeal lymphatic skull microchannels, provide multiple routes interaction between system, addition blood vasculature. In this Review, we describe current ideas about their implications aging, diseases, immune-based therapeutic approaches.

Language: Английский

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The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Feb. 1, 2023

Alzheimer's disease (AD), the most common cause of dementia, results in a sustained decline cognition. There are currently few effective modifying therapies for AD, but insights into mechanisms that mediate onset and progression may lead to new, therapeutic strategies. Amyloid beta oligomers plaques, tau aggregates, neuroinflammation play critical role neurodegeneration impact clinical AD progression. The upstream modulators these pathological features have not been fully clarified, recent evidence indicates gut microbiome (GMB) an influence on therefore human patients. In this review, we summarize studies identified alterations GMB correlate with pathophysiology patients mouse models. Additionally, discuss findings manipulations models potential GMB-targeted therapeutics AD. Lastly, diet, sleep, exercise as modifiers relationship between conclude future directions recommendations further topic.

Language: Английский

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Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Language: Английский

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