Nitric oxide signaling in health and disease

Cell, Год журнала: 2022, Номер 185(16), С. 2853 - 2878

Опубликована: Авг. 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.

Язык: Английский

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Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Июль 11, 2023

Abstract Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large small vessels a key driver of age-related decline. Severe VCID includes post-stroke dementia, subcortical ischemic multi-infarct mixed dementia. While acknowledged as the second most common form after Alzheimer’s disease (AD) accounting for 20% cases, AD frequently coexist. In VCID, vessel (cSVD) often affects arterioles, capillaries, venules, where arteriolosclerosis amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent infarcts, lacunes presumed origin, enlarged perivascular space, microbleeds, brain atrophy neuroimaging hallmarks cSVD. The current primary approach to cSVD treatment control risk factors such hypertension, dyslipidemia, diabetes, smoking. However, causal therapeutic strategies have not been established partly due heterogeneous pathogenesis this review, we summarize pathophysiology discuss probable etiological pathways focusing on hypoperfusion/hypoxia, blood–brain barriers (BBB) dysregulation, fluid drainage disturbances, inflammation define potential diagnostic targets

Язык: Английский

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Nitric Oxide/Nitric Oxide Synthase System in the Pathogenesis of Neurodegenerative Disorders—An Overview

Antioxidants, Год журнала: 2023, Номер 12(3), С. 753 - 753

Опубликована: Март 20, 2023

Nitric oxide, a ubiquitous molecule found throughout the natural world, is key implicated in many central and benefic molecular pathways has well-established role function of nervous system, as numerous studies have previously shown. Dysregulation its metabolism, mainly upregulation nitric oxide production, been proposed trigger and/or aggravator for neurological affections. Increasing evidence supports implication this prevalent neurodegenerative diseases, such Parkinson’s disease, Alzheimer’s or amyotrophic lateral sclerosis. The mechanisms neurotoxicity center around increased quantities that are produced brain, their cause, and, most importantly, pathological metabolic cascades created. These lead to formation neuronal toxic substances impair neurons’ structure on multiple levels. purpose review present main causes well important pathophysiological triggered by could help explain part complex picture diseases develop targeted therapies.

Язык: Английский

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

Free Radical Biology and Medicine, Год журнала: 2022, Номер 194, С. 71 - 83

Опубликована: Ноя. 24, 2022

Язык: Английский

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Two decades of astrocytes in neurovascular coupling

Frontiers in Network Physiology, Год журнала: 2023, Номер 3

Опубликована: Апрель 3, 2023

The brain is a highly energy demanding organ, which accounts in humans for the 20% of total consumption at resting state although comprising only 2% body mass. necessary delivery nutrients to parenchyma ensured by cerebral circulatory system, through exchange glucose and oxygen (O

Язык: Английский

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The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 21, 2024

Neurovascular coupling (NVC) is an important mechanism to ensure adequate blood supply active neurons in the brain. NVC damage can lead chronic impairment of neuronal function. Diabetes characterized by high sugar and considered risk factor for cognitive impairment. In this review, we provide fMRI evidence diabetic patients with decline. Combined exploration major mechanisms signaling pathways NVC, discuss effects hyperglycemia on cellular structure signaling, including key receptors, ion channels, intercellular connections. Studying these diabetes-related changes cell will help us understand underlying causes behind diabetes-induced early decline, ultimately helping identify most effective drug targets treatment.

Язык: Английский

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Unveiling the Interplay: Neurovascular Coupling, Astrocytes and G Protein-Coupled Receptors in Alzheimer’s Disease

ACS Pharmacology & Translational Science, Год журнала: 2025, Номер 8(2), С. 271 - 285

Опубликована: Янв. 8, 2025

Astrocytes are a type of glial cell that involved in actively modulating synaptic plasticity, neurotransmitter homeostasis, and neuroinflammatory responses. More importantly, they coordinate neuronal activity cerebral blood flow (CBF) what is known as neurovascular coupling (NVC). NVC an essential mechanism maintains the high energy demand brain requires by supplying continuous rapid supply oxygen nutrients through CBF. Impairment one key events triggers spiral occurrences lead to clinical advancement Alzheimer's disease (AD). It yet be determined molecular manifestations impairment relate to; nonetheless, it believed alterations G protein-coupled receptors (GPCRs) responsible for exacerbating these effects. In this review, we summarize current evidence supporting involvement GPCRs on astrocytes pathophysiology AD. Additionally, propose potential research directions further elucidate underlying mechanisms evaluate feasibility targeting specific therapeutic strategy correct memory impairments associated with

Язык: Английский

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Mitochondrial Ca2+ handling as a cell signaling hub: lessons from astrocyte function

Essays in Biochemistry, Год журнала: 2023, Номер 67(1), С. 63 - 75

Опубликована: Янв. 13, 2023

Abstract Astrocytes are a heterogenous population of macroglial cells spread throughout the central nervous system with diverse functions, expression signatures, and intricate morphologies. Their subcellular compartments contain distinct range mitochondria, functional microdomains exhibiting widespread activities, such as controlling local metabolism Ca2+ signaling. is an ion utmost importance, both physiologically pathologically, participates in critical processes, including synaptic plasticity, neuron–astrocyte integration, excitotoxicity, mitochondrial physiology metabolism. The handling formed by uniporter complex (MCUc), which mediates influx, Na+/Ca2+ exchanger (NCLX), responsible for most efflux, well additional components, permeability transition pore (mtPTP). Over last decades, has been shown to be key brain homeostasis, acting centrally physiopathological processes astrogliosis, astrocyte–neuron activity energy control, neurodegeneration. In this review, we discuss current state knowledge regarding molecular composition, highlighting its impact on astrocytic homeostasis.

Язык: Английский

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Neonatal Anesthesia and Oxidative Stress

Antioxidants, Год журнала: 2022, Номер 11(4), С. 787 - 787

Опубликована: Апрель 16, 2022

Neonatal anesthesia, while often essential for surgeries or imaging procedures, is accompanied by significant risks to redox balance in the brain due relatively weak antioxidant system children. Oxidative stress characterized concentrations of reactive oxygen species (ROS) that are elevated beyond what can be accommodated defense system. In neonatal this has been proposed a contributing factor some negative consequences (e.g., learning deficits and behavioral abnormalities) associated with early anesthetic exposure. order assess relationship between anesthesia oxidative stress, we first review mechanisms action common agents, key pathways produce majority ROS, main antioxidants. We then explore possible immediate, short-term, long-term neonatal-anesthesia-induced stress. large body literature describing evident during immediately following anesthesia. Moreover, our suggests short-term pathway temporally limited effect on manifest years later altered development neurons neurovascular interactions.

Язык: Английский

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Calcium transients in nNOS neurons underlie distinct phases of the neurovascular response to barrel cortex activation in awake mice

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2023, Номер 43(10), С. 1633 - 1647

Опубликована: Май 7, 2023

Neuronal nitric oxide (NO) synthase (nNOS), a Ca 2+ dependent enzyme, is expressed by distinct populations of neocortical neurons. Although neuronal NO well known to contribute the blood flow increase evoked neural activity, relationships between nNOS neurons activity and vascular responses in awake state remain unclear. We imaged barrel cortex awake, head-fixed mice through chronically implanted cranial window. The indicator GCaMP7f was selectively using adenoviral gene transfer cre mice. Air-puffs directed at contralateral whiskers or spontaneous motion induced transients 30.2 ± 2.2% 51.6 3.3% neurons, respectively, local arteriolar dilation. greatest dilatation (14.8 1.1%) occurred when whisking simultaneously. individual dilation showed various degrees correlation, which strongest whole neuron ensemble examined. also found that some became active immediately prior dilation, while others were activated gradually after dilatation. Discrete subsets may either initiation maintenance response, suggesting previously unappreciated temporal specificity role neurovascular coupling.

Язык: Английский

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