The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

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Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia

Pharmacological Reports ◽

10.1007/s43440-021-00269-5 ◽

2021 ◽

Author(s):

Katarzyna Chamera ◽

Magdalena Szuster-Głuszczak ◽

Agnieszka Basta-Kaim

Keyword(s):

Experimental Studies ◽

Physiological Processes ◽

Unique System ◽

The Family ◽

Inflammatory Processes ◽

The Central Nervous System ◽

G Protein Coupled ◽

The Brain ◽

Brain Homeostasis

AbstractSchizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1–CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1–CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1–CX3CR1 dysfunctions in the course of schizophrenia.

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Role of GPR39 in Neurovascular Homeostasis and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22158200 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8200

Author(s):

Yifan Xu ◽

Anthony P. Barnes ◽

Nabil J. Alkayed

Keyword(s):

Central Nervous System ◽

Immune Response ◽

Vascular Tone ◽

Neuronal Excitability ◽

G Protein Coupled Receptors ◽

Constitutive Activity ◽

Biased Signaling ◽

The Central Nervous System ◽

G Protein Coupled

GPR39, a member of the ghrelin family of G protein-coupled receptors, is zinc-responsive and contributes to the regulation of diverse neurovascular and neurologic functions. Accumulating evidence suggests a role as a homeostatic regulator of neuronal excitability, vascular tone, and the immune response. We review GPR39 structure, function, and signaling, including constitutive activity and biased signaling, and summarize its expression pattern in the central nervous system. We further discuss its recognized role in neurovascular, neurological, and neuropsychiatric disorders.

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Emerging Roles of Extracellular Vesicles in the Central Nervous System: Physiology, Pathology, and Therapeutic Perspectives

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.626043 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yadaly Gassama ◽

Alexandre Favereaux

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Extracellular Vesicles ◽

Cell Types ◽

Cellular Processes ◽

Pathological Conditions ◽

The Central Nervous System ◽

System Physiology ◽

The Brain

Extracellular vesicles or EVs are secreted by most, if not all, eukaryote cell types and recaptured by neighboring or distant cells. Their cargo, composed of a vast diversity of proteins, lipids, and nucleic acids, supports the EVs’ inter-cellular communication. The role of EVs in many cellular processes is now well documented both in physiological and pathological conditions. In this review, we focus on the role of EVs in the central nervous system (CNS) in physiological as well as pathological conditions such as neurodegenerative diseases or brain cancers. We also discuss the future of EVs in clinical research, in particular, their value as biomarkers as well as innovative therapeutic agents. While an increasing number of studies reveal EV research as a promising field, progress in the standardization of protocols and innovation in analysis as well as in research tools is needed to make a breakthrough in our understanding of their impact in the pathophysiology of the brain.

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Recent advances in understanding neuropathic pain: glia, sex differences, and epigenetics

F1000Research ◽

10.12688/f1000research.9621.1 ◽

2016 ◽

Vol 5 ◽

pp. 2743 ◽

Cited By ~ 20

Author(s):

Halina Machelska ◽

Melih Ö. Celik

Keyword(s):

Nervous System ◽

Neuropathic Pain ◽

Neuronal Damage ◽

G Protein Coupled Receptors ◽

The Central Nervous System ◽

Non Coding Rnas ◽

Underlying Mechanisms ◽

G Protein Coupled ◽

Epigenetic Processes

Neuropathic pain results from diseases or trauma affecting the nervous system. This pain can be devastating and is poorly controlled. The pathophysiology is complex, and it is essential to understand the underlying mechanisms in order to identify the relevant targets for therapeutic intervention. In this article, we focus on the recent research investigating neuro-immune communication and epigenetic processes, which gain particular attention in the context of neuropathic pain. Specifically, we analyze the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the modulation of the central nervous system inflammation triggered by neuropathy. Considering epigenetics, we address DNA methylation, histone modifications, and the non-coding RNAs in the regulation of ion channels, G-protein-coupled receptors, and transmitters following neuronal damage. The goal was not only to highlight the emerging concepts but also to discuss controversies, methodological complications, and intriguing opinions.

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Histamine, Metabolic Remodelling and Angiogenesis: A Systems Level Approach

Biomolecules ◽

10.3390/biom11030415 ◽

2021 ◽

Vol 11 (3) ◽

pp. 415

Author(s):

Aurelio A. Moya-García ◽

Almudena Pino-Ángeles ◽

Francisca Sánchez-Jiménez ◽

José Luis Urdiales ◽

Miguel Ángel Medina

Keyword(s):

Research Field ◽

G Protein Coupled Receptors ◽

Signalling Pathways ◽

Histamine Metabolism ◽

Current Information ◽

Physiological Processes ◽

Cell Growth And Differentiation ◽

G Protein Coupled

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. Histamine metabolism conforms a very complex network that connect many metabolic processes important for homeostasis, including nitrogen and energy metabolism. This review brings together and analyses the current information on the relationships of the “histamine system” with other important metabolic modules in human physiology, aiming to bridge current information gaps. In this regard, the molecular characterization of the role of histamine in the modulation of angiogenesis-mediated processes, such as cancer, makes a promising research field for future biomedical advances.

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Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

Nature Communications ◽

10.1038/s41467-021-23050-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yuya Yoshida ◽

Naoya Matsunaga ◽

Takaharu Nakao ◽

Kengo Hamamura ◽

Hideaki Kondo ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Clock Genes ◽

Serum Levels ◽

Serum Retinol ◽

Cardiac Inflammation ◽

Physiological Processes ◽

G Protein Coupled ◽

Clock Protein

AbstractDysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure.

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Adipokines and coronary artery disease

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2012.117 ◽

2015 ◽

Vol 78 (3) ◽

Author(s):

Teresa Strisciuglio ◽

Gennaro Galasso ◽

Dario Leosco ◽

Roberta De Rosa ◽

Giuseppe Di Gioia ◽

...

Keyword(s):

Coronary Artery Disease ◽

Adipose Tissue ◽

Coronary Artery ◽

Scientific Evidence ◽

Behavioral Strategies ◽

Physiological Processes ◽

Pathological Conditions ◽

Artery Disease ◽

Pleiotropic Function

Adipose tissue, besides being an important energetic storage, is also a source of cytokines and hormones which act in a paracrine, autocrine and especially endocrine manner, influencing the cardiometabolic axis. Adipokines are a group of mediators with pleiotropic function, that are involved in many physiological processes, so that a disregulation in their secretion can lead to multiple pathological conditions. In this review our aim was to clarify the role of adipokines in the pathogenesis of atherosclerosis, especially in coronary artery disease, and based on current scientific evidence, to analyze the therapeutic and behavioral strategies that are so far available.

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Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

Journal of Pathogens ◽

10.1155/2018/9541987 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Neil N. Patel ◽

Alan D. Workman ◽

Noam A. Cohen

Keyword(s):

Airway Epithelium ◽

Taste Receptor ◽

Upper Airway ◽

Airway Disease ◽

G Protein Coupled Receptors ◽

Innate Immune ◽

Taste Receptors ◽

Taste Sensation ◽

G Protein Coupled

Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease.

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Compartmentalization of GPCR signalling controls unique cellular responses

Biochemical Society Transactions ◽

10.1042/bst20150236 ◽

2016 ◽

Vol 44 (2) ◽

pp. 562-567 ◽

Cited By ~ 27

Author(s):

Andrew M. Ellisdon ◽

Michelle L. Halls

Keyword(s):

Drug Discovery ◽

Drug Targets ◽

Cell Types ◽

G Protein Coupled Receptors ◽

Attrition Rates ◽

Physiological Processes ◽

Simple Chain ◽

G Protein Coupled ◽

Major Drug ◽

Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

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