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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The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity

Chemical Reviews, Год журнала: 2021, Номер 121(24), С. 14682 - 14905

Опубликована: Дек. 13, 2021

Nitric oxide (NO) is an important signaling molecule that involved in a wide range of physiological and pathological events biology. Metal coordination chemistry, especially with iron, at the heart many biological transformations involving NO. A series heme proteins, nitric synthases (NOS), soluble guanylate cyclase (sGC), nitrophorins, are responsible for biosynthesis, sensing, transport Alternatively, NO can be generated from nitrite by heme- copper-containing reductases (NIRs). The NO-bearing small molecules such as nitrosothiols dinitrosyl iron complexes (DNICs) serve alternative vehicle storage transport. Once formed, rich reaction chemistry leads to variety activities including reduction or non-heme iron-containing protein post-translational modifications DNICs. Much our understanding reactivity metal sites biology mechanisms these has come elucidation geometric electronic structures chemical synthetic model systems, synergy biochemical biophysical studies on relevant proteins themselves. This review focuses recent advancements not only have improved roles but also provided foundations biomedical research bio-inspired catalyst design energy science.

Язык: Английский

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Blood–Brain Barrier Permeable Photoacoustic Probe for High-Resolution Imaging of Nitric Oxide in the Living Mouse Brain

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 7952 - 7961

Опубликована: Март 31, 2023

Alternations in the brain nitric oxide (NO) homeostasis are associated with a variety of neurodegeneration diseases; therefore, high-resolution imaging NO is essential for understanding pathophysiological processes. However, currently available probes unsuitable this purpose due to their poor ability cross blood–brain barrier (BBB) or image deep tissues spatial resolution. Herein, we developed photoacoustic (PA) probe BBB crossing overcome obstacle. The shows highly selective ratiometric response toward NO, which enables micron resolution whole living mice. Using three-dimensional PA imaging, demonstrated that could be used visualize detailed distribution varying depth cross-sections (0–8 mm) Parkinson's disease (PD) mouse brain. We also investigated therapeutic properties natural polyphenols PD using as an agent and suggested potential screening agents. This study provides promising high anticipate these findings may open up new possibilities biological functions development agents diagnosis treatment diseases.

Язык: Английский

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Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(1)

Опубликована: Янв. 1, 2025

ABSTRACT Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions individuals. These characterized by pathological changes in various brain regions, specific genetic mutations associated with disease, deposits abnormal proteins, degeneration neurological cells. As neurodegenerative disorders vary their epidemiological characteristics vulnerability neurons, treatment these is usually aimed at slowing disease progression. The heterogeneity environmental factors involved process neurodegeneration makes current methods inadequate. However, existence common molecular mechanisms pathogenesis may allow development new targeted therapeutic strategies. Oxidative nitrosative stress damages membrane components accumulating ROS RNS disrupting redox balance. This results induction apoptosis, which important through oxidative stress. Studies conducted using postmortem human samples, animal models, cell cultures demonstrated stress, apoptosis crucial such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, Huntington's disease. excessive production reactive oxygen nitrogen species, elevated levels free radicals, heightened mitochondrial disturbances energy metabolism, oxidation nitrosylation cellular macromolecules recognized triggers neuronal death. Challenges managing treating require better understanding this field level. Therefore, review elaborates apoptosis.

Язык: Английский

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Nitric oxide signalling in the brain and its control of bodily functions

British Journal of Pharmacology, Год журнала: 2019, Номер 177(24), С. 5437 - 5458

Опубликована: Июль 26, 2019

Nitric oxide (NO) is a versatile molecule that plays key roles in the development and survival of mammalian species by endowing brain neuronal networks with ability to make continual adjustments function response moment‐to‐moment changes physiological input. Here, we summarize progress field argue NO‐synthetizing neurons NO signalling provide core hub for integrating sensory‐ homeostatic‐related cues, control bodily functions, potential target new therapeutic opportunities against several neuroendocrine behavioural abnormalities.

Язык: Английский

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The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2020, Номер unknown

Опубликована: Июнь 9, 2020

Abstract Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and failure in certain cases could be of extra-pulmonary origin. Hypothalamic neural circuits play key roles sex differences, diabetes, hypertension, obesity aging, all risk factors for besides being connected to olfactory/gustative brainstem cardiorespiratory centers. Here, human brain gene-expression analyses immunohistochemistry reveal that the hypothalamus associated regions express angiotensin-converting enzyme transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, correlation genes or pathways involved physiological functions viral pathogenesis. A post-mortem patient shows invasion replication both olfactory bulb hypothalamus, while animal studies indicate hormones metabolic diseases influence this susceptibility.

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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Unveiling the Immune Landscape of Delirium through Single‐Cell RNA Sequencing and Machine Learning: Towards Precision Diagnosis and Therapy

Psychogeriatrics, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 1, 2025

Abstract Background Postoperative delirium (POD) poses significant clinical challenges regarding its diagnosis and treatment. Identifying biomarkers that can predict diagnose POD is crucial for improving patient outcomes. Methods To explore potential POD, we conducted bulk RNA sequencing (bulk‐seq) on peripheral blood samples from patients healthy controls. The expression levels of genes downstream the phosphatidylinositol 3‐kinase/protein kinase B (PI3K‐Akt) signalling pathway were analysed. We then validated these using quantitative real‐time polymerase chain reaction (RT‐qPCR) in an independent cohort 30 controls patients. Receiver operating characteristic (ROC) analysis six machine learning models used to evaluate predictive diagnostic value genes. Additionally, single‐cell (scRNA‐seq) was performed validate gene specific subsets mononuclear cells (PBMCs), including T‐cells, B‐cells, natural killer (NK) cells, dendritic (DCs), monocytes. Results Bulk‐seq revealed increased PI3K‐Akt pathway, specifically CHRM2 , IL6 NOS3 NGF IL6R compared Conversely, IGF1 significantly decreased. RT‐qPCR validation confirmed findings. ROC indicated are useful predicting diagnosing POD. scRNA‐seq further PBMC subsets, NK DCs, monocytes, with results consistent bulk‐seq data. Conclusions abnormal activation monocytes may serve as These findings could inform development novel therapeutic strategies managing

Язык: Английский

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NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice

Science Translational Medicine, Год журнала: 2022, Номер 14(665)

Опубликована: Окт. 5, 2022

The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role the regulation of secretion gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that disruption neuronal NO synthase (NOS1) activity underlies some forms hypogonadotropic hypogonadism. Whole-exome sequencing was performed on cohort 341 probands with congenital hypogonadism to identify ultrarare variants NOS1 . identified mutant proteins assessed by their ability promote nitrite and cGMP production vitro. In addition, physiological pharmacological characterization carried out Nos1 -deficient mouse model. five heterozygous loss-of-function mutations six (2%), who displayed additional phenotypes including anosmia, hearing loss, intellectual disability. found be transiently expressed GnRH nose both humans mice, deficiency mice resulted dose-dependent defects sexual maturation as well olfaction, hearing, cognition. inhibition postnatal revealed critical time window during shaped minipuberty maturation. Inhaled treatment at rescued reproductive behavioral mice. summary, lack led associated sensory comorbidities reversed deficits maturation, cognition suggesting potential therapy deficiency.

Язык: Английский

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New Horizons: Gonadotropin-Releasing Hormone and Cognition

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2023, Номер 108(11), С. 2747 - 2758

Опубликована: Июнь 1, 2023

Abstract Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function hypothalamic–pituitary–gonadal axis, which controls onset puberty fertility. Two recent studies suggest that, in addition to controlling reproduction, neurons brain that produce GnRH are also involved control postnatal maturation, odor discrimination, adult cognition. This review will summarize development establishment system, with particular attention importance its first activation, a phenomenon known as minipuberty, later reproductive nonreproductive functions. In addition, we discuss beneficial effects restoring physiological (ie, pulsatile) levels on olfactory cognitive alterations preclinical Down syndrome Alzheimer disease models, well potential risks associated long-term continuous nonphysiological) administration certain disorders. Finally, this addresses intriguing possibility pulsatile therapy may hold therapeutic management some neurodevelopmental disorders pathological aging elderly people.

Язык: Английский

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