Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(9), P. 609 - 633

Published: July 24, 2020

Language: Английский

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Immunological mechanisms of vaccine-induced protection against COVID-19 in humans

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(8), P. 475 - 484

Published: July 1, 2021

Language: Английский

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The spectrum of inflammatory responses

Science, Journal Year: 2021, Volume and Issue: 374(6571), P. 1070 - 1075

Published: Nov. 25, 2021

Inflammation is an integral part of animal biology. It provides critical protection from adverse environmental factors by enforcing the defense homeostasis and functional structural integrity tissues organs. Recent advances have uncovered a broad range biological processes that involve inflammatory control, calling for renewed framework inflammation beyond its classical roles in infection injury. In this Review, new perspectives on biology are discussed research directions suggested to address fundamental gaps our current understanding.

Language: Английский

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T cells with dysfunctional mitochondria induce multimorbidity and premature senescence

Science, Journal Year: 2020, Volume and Issue: 368(6497), P. 1371 - 1376

Published: May 21, 2020

The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators senescence. mice, these instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result in premature death. cell metabolic failure induces the accumulation circulating cytokines, resembles chronic inflammation is characteristic aging ("inflammaging"). This cytokine storm itself acts a systemic inducer Blocking tumor necrosis factor-α signaling or preventing senescence nicotinamide adenine dinucleotide precursors partially rescues mice

Language: Английский

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Hallmarks of Health

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 33 - 63

Published: Dec. 18, 2020

Language: Английский

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The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 74(3), P. 670 - 685

Published: Dec. 7, 2020

Acute decompensation (AD) of cirrhosis is defined by the development ascites, hepatic encephalopathy and/or variceal bleeding. Ascites traditionally attributed to splanchnic arterial vasodilation and left ventricular dysfunction, hyperammonaemia, haemorrhage portal hypertension. Recent large-scale European observational studies have shown that systemic inflammation a hallmark AD. Here we present working hypothesis, suggesting through an impairment functions one or more major organ systems may be common theme act synergistically with traditional mechanisms involved in Systemic impair system function which are not mutually exclusive. The first mechanism nitric oxide-mediated accentuation preexisting vasodilation, resulting overactivation endogenous vasoconstrictor elicit intense vasoconstriction hypoperfusion certain vascular beds, particular renal circulation. Second, cause immune-mediated tissue damage, process called immunopathology. Finally, induce important metabolic changes. Indeed, inflammatory responses energetically expensive processes, requiring reallocation nutrients (glucose, amino acids lipids) fuel immune activation. also inhibits nutrient consumption peripheral (non-immune) organs, effect provide prioritisation fuels for responses. However, decrease organs result decreased mitochondrial production ATP (energy) subsequently impaired function.

Language: Английский

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Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF

Journal of Hepatology, Journal Year: 2019, Volume and Issue: 72(4), P. 688 - 701

Published: Nov. 25, 2019

Language: Английский

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Albumin in decompensated cirrhosis: new concepts and perspectives

Gut, Journal Year: 2020, Volume and Issue: 69(6), P. 1127 - 1138

Published: Feb. 26, 2020

The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays major role in the development multiorgan dysfunction. Such abnormality mainly due to spread bacteria and/or bacterial products from gut danger-associated molecular patterns diseased liver triggering release mediators activating immune cells. exacerbation these processes underlies acute-on-chronic failure. A further mechanism promoting dysfunction failure likely consists with mitochondrial oxidative phosphorylation responsible for cellular energy crisis. state patients also structural functional changes albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating endothelium protective functions. knowledge abnormalities provides novel targets mechanistic treatments. In this respect, oncotic make it potential multitarget agent. This would expand well-established indications use cirrhosis, aim at improving effective volaemia or preventing deterioration. Evidence has been recently provided long-term administration ascites improves survival, prevents complications, eases management reduces hospitalisations. However, variant results indicate investigations are needed, aiming confirming beneficial effects albumin, clarifying optimal dosage schedule identify who benefit most administration.

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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Tissue Homeostasis and Inflammation

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 557 - 581

Published: March 2, 2021

There is a growing interest in understanding tissue organization, homeostasis, and inflammation. However, despite an abundance of data, the organizing principles biology remain poorly defined. Here, we present perspective on organization based relationships between cell types functions that they perform. We provide formal definition homeostasis as collection circuits regulate specific variables within environment, describe how functional tissues allows for maintenance both systemic homeostasis. This leads to natural inflammation response deviations from cannot be reversed by homeostatic mechanisms alone. inflammatory signals act same cellular involved normal order coordinate emergency responses perturbations ultimately return system state. Finally, consider hierarchy implications development diseases.

Language: Английский

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