Nitric oxide signaling in health and disease

Cell, Journal Year: 2022, Volume and Issue: 185(16), P. 2853 - 2878

Published: Aug. 1, 2022

The surprising discovery that the diatomic gas nitric oxide (NO) is generated by mammalian cells and serves to regulate a multitude of physiological processes has continued fascinate biologists for almost four decades. biochemistry NO complex, novel insights into control biosynthesis mechanisms signal transduction are continuously emerging. key regulator cardiovascular function, metabolism, neurotransmission, immunity, more, aberrant signaling central feature many major disorders including disease, diabetes, cancer. Here, we discuss basics biology emphasizing recent advances in field means increasing bioactivity with therapeutic nutritional implications.

Language: Английский

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Revisiting the neurovascular unit

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(9), P. 1198 - 1209

Published: Aug. 5, 2021

Language: Английский

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Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(1), P. 31 - 276

Published: April 18, 2022

Over the last two decades, hydrogen sulfide (H2S) has emerged as an endogenous regulator of a broad range physiological functions. H2S belongs to class molecules known gasotransmitters, which typically include nitric oxide (NO) and carbon monoxide (CO). Three enzymes are recognized sources in various cells tissues: cystathionine γ-lyase (CSE), β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST). The present article reviews regulation these well pathways their enzymatic nonenzymatic degradation elimination. multiple interactions with other labile (e.g., NO) reactive oxygen species also outlined. Next, biological targets signaling outlined, special reference or oxidative posttranscriptional modification (persulfidation sulfhydration) proteins effect on channels intracellular second messenger pathways, gene transcription translation, cellular bioenergetics metabolism. pharmacological molecular tools currently available study physiology reviewed, including utility limitations. In subsequent sections, role functions is membrane potential, endo- exocytosis, cell organelles (endoplasmic reticulum, Golgi, mitochondria), movement, cycle, differentiation, aspects regulated death. roles types organ systems overviewed, red blood cells, immune central peripheral nervous (with focus neuronal transmission, learning, memory formation), vascular function (including angiogenesis its specialized cerebrovascular, renal, pulmonary beds) senses, vision, hearing, taste smell, pain-sensing. Finally, (lung, heart, liver, kidney, urogenital organs, reproductive system, bone cartilage, skeletal muscle, endocrine organs) presented, aging) but extending some common pathophysiological conditions. From data, wide array significant all emerges characteristic bell-shaped biphasic effects highlighted. addition, key aspects, debated areas, future research translational areas identified.

Language: Английский

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The “Neuro-Glial-Vascular” Unit: The Role of Glia in Neurovascular Unit Formation and Dysfunction

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Sept. 27, 2021

The neurovascular unit (NVU) is a complex multi-cellular structure consisting of endothelial cells (ECs), neurons, glia, smooth muscle (SMCs), and pericytes. Each component closely linked to each other, establishing structural functional unit, regulating central nervous system (CNS) blood flow energy metabolism as well forming the blood-brain barrier (BBB) inner blood-retina (BRB). As name suggests, "neuro" "vascular" components NVU are recognized coupling key function NVU. However, consists multiple cell types its functionality goes beyond resulting coupling, with cross-component links signaling, metabolism, homeostasis. Within NVU, glia have gained increased attention it increasingly clear that they fulfill various multi-level functions in Glial dysfunctions were shown precede neuronal vascular pathologies suggesting roles for pathogenesis disease. In this review, we take "glio-centric" view on development retina brain, how these change disease, advancing experimental techniques will help us address unanswered questions.

Language: Английский

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Losing the dogmatic view of cerebral autoregulation

Physiological Reports, Journal Year: 2021, Volume and Issue: 9(15)

Published: July 28, 2021

In 1959, Niels Lassen illustrated the cerebral autoregulation curve in classic review article entitled Cerebral Blood Flow and Oxygen Consumption Man. This concept suggested a relatively broad mean arterial pressure range (~60–150 mmHg) wherein blood flow remains constant. However, assumption that this wide plateau could be applied on within-individual basis is incorrect greatly variable between individuals. Indeed, each data point autoregulatory originated from independent samples of participants patients represented interindividual relationships pressure. Nonetheless, influential commonly cited various high-impact publications medical textbooks, frequently taught science education without appropriate nuances caveats. Herein, we provide rationale additional experimental supporting notion need to lose dogmatic view autoregulation.

Language: Английский

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Neurovascular coupling mechanisms in health and neurovascular uncoupling in Alzheimer’s disease

Brain, Journal Year: 2022, Volume and Issue: 145(7), P. 2276 - 2292

Published: May 13, 2022

Abstract To match the metabolic demands of brain, mechanisms have evolved to couple neuronal activity vasodilation, thus increasing local cerebral blood flow and delivery oxygen glucose active neurons. Rather than relying on feedback signals such as consumption or glucose, main signalling pathways rely release vasoactive molecules by neurons astrocytes, which act contractile cells. Vascular smooth muscle cells pericytes are associated with arterioles capillaries, respectively, relax induce vasodilation. Much progress has been made in understanding complex neurovascular coupling, but issues contributions capillary astrocyte calcium signal remain contentious. Study coupling is especially important dysregulation a prominent feature Alzheimer’s disease. In this article we will discuss developments controversies finish discussing current knowledge concerning uncoupling

Language: Английский

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The contribution of an imbalanced redox signalling to neurological and neurodegenerative conditions

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 194, P. 71 - 83

Published: Nov. 24, 2022

Language: Английский

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Exhaled Nitric Oxide as Biomarker of Type 2 Diseases

Cells, Journal Year: 2023, Volume and Issue: 12(21), P. 2518 - 2518

Published: Oct. 25, 2023

Nitric oxide (NO) is a short-lived gas molecule which has been studied for its role as signaling in the vasculature and later, broader view, cellular messenger many other biological processes such immunity inflammation, cell survival, apoptosis, aging. Fractional exhaled nitric (FeNO) convenient, easy-to-obtain, non-invasive method assessing active, mainly Th2-driven, airway sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves valued tool aid diagnosis monitoring of several asthma phenotypes. More recently, evaluated respiratory and/or immunological conditions, including allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, atopic dermatitis, eosinophilic esophagitis, food allergy. In this review, we aim provide an extensive overview current state knowledge about biomarker type 2 outlining past recent data on application measurement patients affected by broad variety atopic/allergic disorders.

Language: Английский

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Long-range inhibitory neurons mediate cortical neurovascular coupling

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 113970 - 113970

Published: March 19, 2024

To meet the high energy demands of brain function, cerebral blood flow (CBF) parallels changes in neuronal activity by a mechanism known as neurovascular coupling (NVC). However, which neurons play role mediating NVC is not well understood. Here, we identify mice and humans specific population cortical GABAergic that co-express nitric oxide synthase tachykinin receptor 1 (Tacr1). Through whole-tissue clearing, demonstrate Tacr1 extend local long-range projections across functionally connected areas. We show whisker stimulation elicited neuron barrel cortex through feedforward excitatory pathways. Additionally, optogenetic experiments, are instrumental CBF relaxation mural cells similar fashion to stimulation. Finally, electron microscopy, observe processes contact astrocytic endfeet. These findings suggest integrate mediate NVC.

Language: Английский

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Nitric Oxide Pathways in Neurovascular Coupling Under Normal and Stress Conditions in the Brain: Strategies to Rescue Aberrant Coupling and Improve Cerebral Blood Flow

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 22, 2021

The brain has impressive energy requirements and paradoxically, very limited reserves, implying its huge dependency on continuous blood supply. Aditionally, cerebral flow must be dynamically regulated to the areas of increased neuronal activity thus, metabolic demands. coupling between (CBF) is supported by a mechanism called neurovascular (NVC). Among several vasoactive molecules released glutamatergic activation, nitric oxide ( • NO) recognized key player in process essential for development response. Classically, NO produced neurons upon activation N -methyl- D -aspartate (NMDA) receptor isoform synthase promotes vasodilation activating soluble guanylate cyclase smooth muscle cells adjacent arterioles. This pathway part more complex network which other molecular cellular intervenients, as well sources NO, are involved. elucidation these interacting mechanisms fundamental understanding how manages failure this translates into dysfunction. Here, we aimed provide an integrated updated perspective role NVC, incorporating most recent evidence that reinforces central from both viewpoints, physiological mediator pathological stressor. First, described glutamate-NMDA receptor-nNOS axis then reviewed link derailment NVC dysfunction associated with neurodegeneration (with focus Alzheimer’s disease). We further discussed oxidative stress dysfunction, specifically decreasing bioavailability diverting bioactivity toward cytotoxicity. Finally, highlighted some strategies targeting rescue or maintenance could explored mitigate neurodegenerative conditions. In line this, potential modulatory effects dietary nitrate polyphenols NO-dependent association physical exercise, may used effective non-pharmacological promote manage neuropathological

Language: Английский

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