Molecular mechanisms and physiological importance of circadian rhythms

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(2), P. 67 - 84

Published: Nov. 25, 2019

Language: Английский

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Role of neuroinflammation in neurodegeneration development

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

Published: July 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Language: Английский

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Microglia: Agents of the CNS Pro-Inflammatory Response

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1717 - 1717

Published: July 17, 2020

The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though research spans over century, last two decades have increased our understanding exponentially. Here, we discuss phenotypic transformation from homeostatic towards reactive microglia, initiated specific ligand binding pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering expressed on myeloid cells-2 (TREM2), as well signaling pathways triggered such caspase-mediated response. Additionally, new disciplines epigenetics and immunometabolism provided us with more holistic view how changes in DNA methylation, microRNAs, metabolome may influence This review aimed current knowledge different angles, recent highlights role exosomes spreading neuroinflammation emerging techniques positron emission tomography (PET) scanning use human generated induced pluripotent stem cells (iPSCs). Finally, also thoughts impact

Language: Английский

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Perfect timing: circadian rhythms, sleep, and immunity — an NIH workshop summary

JCI Insight, Journal Year: 2020, Volume and Issue: 5(1)

Published: Jan. 15, 2020

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate adaptive responses — ranging from leukocyte mobilization, trafficking, chemotaxis to cytokine release T cell differentiation —are mediated time of day–dependent manner. The National Institutes Health (NIH) recently sponsored an interdisciplinary workshop, “Sleep Insufficiency, Circadian Misalignment, the Immune Response,” highlight new research linking biology function identify areas high translational potential. This Review summarizes topics discussed highlights immediate opportunities delineating clinically relevant connections among biological rhythms, sleep, regulation.

Language: Английский

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The circadian immune system

Science Immunology, Journal Year: 2022, Volume and Issue: 7(72)

Published: June 3, 2022

The immune system is highly time-of-day dependent. Pioneering studies in the 1960s were first to identify responses be under a circadian control. Only last decade, however, have molecular factors governing rhythms been identified. These revealed complex picture of interconnectivity rhythmicity within cells with that their environment. Here, we provide global overview system, focusing on recent advances rapidly expanding field immunology.

Language: Английский

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Microbiota–gut–brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(7), P. 2645 - 2673

Published: Jan. 27, 2023

Abstract Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is complex picture genetic environmental factors implicated. Nowadays, gut microbiota in spotlight new research related to this kind psychiatric disorder, as can be consistently several pathophysiological events observed BD. In context so-called microbiota–gut–brain (MGB) axis, shown have strong influence on host neuromodulation endocrine functions (i.e., controlling synthesis neurotransmitters like serotonin or mediating activation hypothalamic–pituitary–adrenal axis), well modulation immune responses, critically regulating intestinal, systemic brain inflammation (neuroinflammation). present review aims elucidate derived from MGB axis disruption possible therapeutic approaches mainly focusing network Understanding its bidirectional communication other systems shed light discovery therapies for improving clinical management these patients. Besides, effect drugs currently used patients, together therapeutical targeting ecosystem (dietary patterns, probiotics, prebiotics, novelties) will also contemplated.

Language: Английский

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Circadian rhythm regulates the function of immune cells and participates in the development of tumors

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 27, 2024

Abstract Circadian rhythms are present in almost all cells and play a crucial role regulating various biological processes. Maintaining stable circadian rhythm is essential for overall health. Disruption of this can alter the expression clock genes cancer-related genes, affect many metabolic pathways factors, thereby affecting function immune system contributing to occurrence progression tumors. This paper aims elucidate regulatory effects BMAL1, other on cells, reveal molecular mechanism rhythm’s involvement tumor its microenvironment regulation. A deeper understanding has potential provide new strategies treatment cancer immune-related diseases.

Language: Английский

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Circadian Rhythm, Microglia-Mediated Neuroinflammation, and Alzheimer’s Disease

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: 170, P. 106044 - 106044

Published: Feb. 4, 2025

Language: Английский

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Chronic low-dose REV-ERBs agonist SR9009 mitigates constant light-induced weight gain and insulin resistance via adipogenesis modulation

Biomedical Journal, Journal Year: 2025, Volume and Issue: unknown, P. 100830 - 100830

Published: Jan. 1, 2025

Obesity and circadian rhythm disruption are significant global health concerns, contributing to an increased risk of metabolic disorders. Both adipose tissue rhythms play critical roles in maintaining energy homeostasis, their dysfunction is closely linked obesity. This study aimed assess the effects chronic low-dose SR9009, a REV-ERB ligand, on induced by constant light exposure mice. Mice were exposed for eight weeks (LL mice), resulting body weight, insulin resistance, white fat mass, altered clock gene expression. Low-dose SR9009 (10 mg/kg daily) was administered chronically its impact these disruptions. LL mice treated with showed reduced weight gain, mass but no overall homeostasis. suppressed Bmal1 expression restored Rev-erbα Rev-erbβ brown (WAT BAT). In vitro studies using 3T3-L1 cells indicated that inhibited adipogenesis, leading further investigation vivo. ChREBP1a Srebp-1c BAT did not affect inflammatory cytokine or adipokine expression, nor it restore Fasn, Pparγ, Prom1 both WAT BAT. These findings suggest may be potential therapeutic preventing gain resistance caused disruptions, likely through adipogenesis inhibition, though other pathways remain limited at low doses.

Language: Английский

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SR9009 has REV-ERB–independent effects on cell proliferation and metabolism

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(25), P. 12147 - 12152

Published: May 24, 2019

The nuclear receptors REV-ERBα and -β link circadian rhythms metabolism. Like other receptors, REV-ERB activity can be regulated by ligands, including naturally occurring heme. A putative ligand, SR9009, has been reported to elicit a range of beneficial effects in healthy as well diseased animal models cell systems. However, the direct involvement REV-ERBs these SR9009 not thoroughly assessed, experiments were performed complete absence both proteins. Here, we report generation mouse model for conditional genetic deletion -β. We show that decrease viability, rewire cellular metabolism, alter gene transcription hepatocytes embryonic stem cells lacking Thus, cannot used solely surrogate activity.

Language: Английский

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