scholarly journals Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1051
Author(s):  
José M. Valdivielso ◽  
Àuria Eritja ◽  
Maite Caus ◽  
Milica Bozic
Keyword(s):  
Signaling Pathways ◽  
Current Knowledge ◽  
Receptor Activation ◽  
Whole Body ◽  
Ionotropic Receptor ◽  
Glomerular Function ◽  
Endocrine Organ ◽  
Downstream Signaling ◽  
Wide Range ◽  
The Central Nervous System

N-Methyl-d-aspartate receptor (NMDAR) is a glutamate-gated ionotropic receptor that intervenes in most of the excitatory synaptic transmission within the central nervous system (CNS). Aside from being broadly distributed in the CNS and having indispensable functions in the brain, NMDAR has predominant roles in many physiological and pathological processes in a wide range of non-neuronal cells and tissues. The present review outlines current knowledge and understanding of the physiological and pathophysiological functions of NMDAR in the kidney, an essential excretory and endocrine organ responsible for the whole-body homeostasis. The review also explores the recent findings regarding signaling pathways involved in NMDAR-mediated responses in the kidney. As established from diverse lines of research reviewed here, basal levels of receptor activation within the kidney are essential for the maintenance of healthy tubular and glomerular function, while a disproportionate activation can lead to a disruption of NMDAR’s downstream signaling pathways and a myriad of pathophysiological consequences.

scholarly journals Reovirus Activates Transforming Growth Factor β and Bone Morphogenetic Protein Signaling Pathways in the Central Nervous System That Contribute to Neuronal Survival following Infection

2009 ◽  
Vol 83 (10) ◽  
pp. 5035-5045 ◽  
Author(s):  
J. David Beckham ◽  
Kathryn Tuttle ◽  
Kenneth L. Tyler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Downstream Signaling ◽  
Morphogenetic Protein ◽  
The Central Nervous System

ABSTRACT Viral infections of the central nervous system (CNS) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. We now show that reovirus infection activates transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling in a murine model of encephalitis in vivo. TGF-β receptor I (TGF-βRI) expression is increased and its downstream signaling factor, SMAD3, is activated in the brains of reovirus-infected mice. TGF-β signaling is neuroprotective, as inhibition with a TGF-βRI inhibitor increases death of infected neurons. Similarly, BMP receptor I expression is increased and its downstream signaling factor, SMAD1, is activated in reovirus-infected neurons in the brains of infected mice in vivo. Activated SMAD1 and SMAD3 were both detected in regions of brain infected by reovirus, but activated SMAD1 was found predominantly in uninfected neurons in close proximity to infected neurons. Treatment of reovirus-infected primary mouse cortical neurons with a BMP agonist reduced apoptosis. These data provide the first evidence for the activation of TGF-β and BMP signaling pathways following neurotropic viral infection and suggest that these signaling pathways normally function as part of the host's protective innate immune response against CNS viral infection.

scholarly journals Novel targets for prostate cancer chemoprevention

2010 ◽  
Vol 17 (3) ◽  
pp. R195-R212 ◽  
Author(s):  
Fazlul H Sarkar ◽  
Yiwei Li ◽  
Zhiwei Wang ◽  
Dejuan Kong
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathways ◽  
Current Knowledge ◽  
Cancer Chemoprevention ◽  
Nuclear Factor Κb ◽  
The United States ◽  
Molecular Signaling ◽  
Downstream Signaling ◽  
Natural Agents ◽  
Cell Signaling Pathways

Among many endocrine-related cancers, prostate cancer (PCa) is the most frequent male malignancy, and it is the second most common cause of cancer-related death in men in the United States. Therefore, this review focuses on summarizing the knowledge of molecular signaling pathways in PCa because, in order to better design new preventive strategies for the fight against PCa, documentation of the knowledge on the pathogenesis of PCa at the molecular level is very important. Cancer cells are known to have alterations in multiple cellular signaling pathways; indeed, the development and the progression of PCa are known to be caused by the deregulation of several selective signaling pathways such as the androgen receptor, Akt, nuclear factor-κB, Wnt, Hedgehog, and Notch. Therefore, strategies targeting these important pathways and their upstream and downstream signaling could be promising for the prevention of PCa progression. In this review, we summarize the current knowledge regarding the alterations in cell signaling pathways during the development and progression of PCa, and document compelling evidence showing that these are the targets of several natural agents against PCa progression and its metastases.

scholarly journals Heparan Sulfate Proteoglycans in Viral Infection and Treatment: A Special Focus on SARS-CoV-2

2021 ◽  
Vol 22 (12) ◽  
pp. 6574
Author(s):  
Valeria De Pasquale ◽  
Miriam Shasa Quiccione ◽  
Simona Tafuri ◽  
Luigi Avallone ◽  
Luigi Michele Pavone
Keyword(s):  
Heparan Sulfate ◽  
Molecular Mechanisms ◽  
Core Protein ◽  
Current Knowledge ◽  
Receptor Activation ◽  
Heparan Sulfate Proteoglycans ◽  
Host Cells ◽  
Special Focus ◽  
Matrix Remodeling ◽  
Wide Range

Heparan sulfate proteoglycans (HSPGs) encompass a group of glycoproteins composed of unbranched negatively charged heparan sulfate (HS) chains covalently attached to a core protein. The complex HSPG biosynthetic machinery generates an extraordinary structural variety of HS chains that enable them to bind a plethora of ligands, including growth factors, morphogens, cytokines, chemokines, enzymes, matrix proteins, and bacterial and viral pathogens. These interactions translate into key regulatory activity of HSPGs on a wide range of cellular processes such as receptor activation and signaling, cytoskeleton assembly, extracellular matrix remodeling, endocytosis, cell-cell crosstalk, and others. Due to their ubiquitous expression within tissues and their large functional repertoire, HSPGs are involved in many physiopathological processes; thus, they have emerged as valuable targets for the therapy of many human diseases. Among their functions, HSPGs assist many viruses in invading host cells at various steps of their life cycle. Viruses utilize HSPGs for the attachment to the host cell, internalization, intracellular trafficking, egress, and spread. Recently, HSPG involvement in the pathogenesis of SARS-CoV-2 infection has been established. Here, we summarize the current knowledge on the molecular mechanisms underlying HSPG/SARS-CoV-2 interaction and downstream effects, and we provide an overview of the HSPG-based therapeutic strategies that could be used to combat such a fearsome virus.

scholarly journals Cross Talk Between Cyclic Nucleotides and Calcium Signaling Pathways in Plants–Achievements and Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Brygida Świeżawska-Boniecka ◽  
Maria Duszyn ◽  
Mateusz Kwiatkowski ◽  
Adriana Szmidt-Jaworska ◽  
Krzysztof Jaworski
Keyword(s):  
Signaling Pathways ◽  
Cross Talk ◽  
Calcium Ions ◽  
Cyclic Nucleotides ◽  
Current Knowledge ◽  
Spatiotemporal Pattern ◽  
Signal Molecules ◽  
Cyclic Nucleotide Gated Channels ◽  
Wide Range ◽  
And Function

A variety of plant cellular activities are regulated through mechanisms controlling the level of signal molecules, such as cyclic nucleotides (cNMPs, e.g., cyclic adenosine 3′:5′-monophosphate, cAMP, and cyclic guanosine 3′:5′- monophosphate, cGMP) and calcium ions (Ca2+). The mechanism regulating cNMP levels affects their synthesis, degradation, efflux and cellular distribution. Many transporters and the spatiotemporal pattern of calcium signals, which are transduced by multiple, tunable and often strategically positioned Ca2+-sensing elements, play roles in calcium homeostasis. Earlier studies have demonstrated that while cNMPs and Ca2+ can act separately in independent transduction pathways, they can interact and function together. Regardless of the context, the balance between Ca2+ and cNMP is the most important consideration. This balance seems to be crucial for effectors, such as phosphodiesterases, cyclic nucleotide gated channels and cyclase activity. Currently, a wide range of molecular biology techniques enable thorough analyses of cellular cross talk. In recent years, data have indicated relationships between calcium ions and cyclic nucleotides in mechanisms regulating specific signaling pathways. The purpose of this study is to summarize the current knowledge on nucleotide-calcium cross talk in plants.

Individual Muscle Contributions to Whole-Body Angular Momentum During Normal Walking

2010 ◽  
Author(s):  
Richard R. Neptune ◽  
Craig P. McGowan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Angular Momentum ◽  
Dynamic Balance ◽  
Whole Body ◽  
Normal Walking ◽  
Complex Dynamic ◽  
Dynamic Task ◽  
Wide Range ◽  
The Central Nervous System

Walking is a complex dynamic task that requires the generation of whole-body angular momentum to maintain dynamic balance and perform a wide range of locomotor tasks. Previous studies have shown that controlling angular momentum is essential to maintaining dynamic balance and preventing falls during walking [1] and recovering from a trip [2]. Others have suggested that angular momentum is highly regulated by the central nervous system [3] and that control synergies may be used to provide this regulation [4].

scholarly journals Lipid Signaling in Ocular Neovascularization

2020 ◽  
Vol 21 (13) ◽  
pp. 4758 ◽  
Author(s):  
Ryo Terao ◽  
Hiroki Kaneko
Keyword(s):  
Signaling Pathways ◽  
Membrane Lipids ◽  
Current Knowledge ◽  
Hypoxia Inducible Factor ◽  
Vascular Diseases ◽  
Corneal Neovascularization ◽  
Lipid Mediators ◽  
Lipid Signaling ◽  
Ocular Neovascularization ◽  
Wide Range

Vasculogenesis and angiogenesis play a crucial role in embryonic development. Pathological neovascularization in ocular tissues can lead to vision-threatening vascular diseases, including proliferative diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, choroidal neovascularization, and corneal neovascularization. Neovascularization involves various cellular processes and signaling pathways and is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF). Modulating these circuits may represent a promising strategy to treat ocular neovascular diseases. Lipid mediators derived from membrane lipids are abundantly present in most tissues and exert a wide range of biological functions by regulating various signaling pathways. In particular, glycerophospholipids, sphingolipids, and polyunsaturated fatty acids exert potent pro-angiogenic or anti-angiogenic effects, according to the findings of numerous preclinical and clinical studies. In this review, we summarize the current knowledge regarding the regulation of ocular neovascularization by lipid mediators and their metabolites. A better understanding of the effects of lipid signaling in neovascularization may provide novel therapeutic strategies to treat ocular neovascular diseases and other human disorders.

scholarly journals Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

2020 ◽  
Author(s):  
Nóra Török ◽  
Masaru Tanaka ◽  
László Vécsei
Keyword(s):  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Kynurenine Pathway ◽  
Neurologic Diseases ◽  
Wide Range ◽  
Treatment Plans ◽  
The Central Nervous System ◽  
Biomarker Research ◽  
Abundant Data

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of the KP alteration observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota to the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

The endocannabinoid system

2020 ◽  
Vol 64 (3) ◽  
pp. 485-499
Author(s):  
Aruna Kilaru ◽  
Kent D. Chapman
Keyword(s):  
Signaling Pathways ◽  
Membrane Lipids ◽  
Endocannabinoid System ◽  
Physiological Processes ◽  
Therapeutic Value ◽  
Wide Range ◽  
Therapeutic Development ◽  
The Central Nervous System ◽  
Psychotropic Effects ◽  
Signaling Process

Abstract Thirty years ago, the discovery of a cannabinoid (CB) receptor that interacts with the psychoactive compound in Cannabis led to the identification of anandamide, an endogenous receptor ligand or endocannabinoid. Research on endocannabinoids has since exploded, and additional receptors along with their lipid mediators and signaling pathways continue to be revealed. Specifically, in humans, the release of endocannabinoids from membrane lipids occurs on demand and the signaling process is rapidly attenuated by the breakdown of the ligand suggesting a tight regulation of the endocannabinoid system (ECS). Additionally, the varying distribution of CB receptors between the central nervous system and other tissues allows for the ECS to participate in a wide range of cognitive and physiological processes. Select plant-derived ‘phyto’cannabinoids such as Δ-9-tetrahydrocannabinol (Δ9-THC) bind to the CB receptors and trigger the ECS, and in the case of Δ9-THC, while it has therapeutic value, can also produce detrimental effects. Current research is aimed at the identification of additional phytocannabinoids with minimal psychotropic effects with potential for therapeutic development. Although decades of research on the ECS and its components have expanded our understanding of the mechanisms and implications of endocannabinoid signaling in mammals, it continues to evolve. Here, we provide a brief overview of the ECS and its overlap with other related lipid-mediated signaling pathways.

scholarly journals Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

2020 ◽  
Vol 21 (24) ◽  
pp. 9338 ◽  
Author(s):  
Nóra Török ◽  
Masaru Tanaka ◽  
László Vécsei
Keyword(s):  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Kynurenine Pathway ◽  
Neurologic Diseases ◽  
Wide Range ◽  
Treatment Plans ◽  
The Central Nervous System ◽  
Biomarker Research ◽  
Abundant Data

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to the abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes, which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of KP alterations observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota in the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

scholarly journals Interplay between BMPs and Reactive Oxygen Species in Cell Signaling and Pathology

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 534 ◽  
Author(s):  
Cristina Sánchez-de-Diego ◽  
José Antonio Valer ◽  
Carolina Pimenta-Lopes ◽  
José Luis Rosa ◽  
Francesc Ventura
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Musculoskeletal Diseases ◽  
Current Knowledge ◽  
Reactive Oxygen ◽  
Membrane Receptors ◽  
Whole Body ◽  
Cell Physiology ◽  
Oxygen Species

The integration of cell extrinsic and intrinsic signals is required to maintain appropriate cell physiology and homeostasis. Bone morphogenetic proteins (BMPs) are cytokines that belong to the transforming growth factor-β (TGF-β) superfamily, which play a key role in embryogenesis, organogenesis and regulation of whole-body homeostasis. BMPs interact with membrane receptors that transduce information to the nucleus through SMAD-dependent and independent pathways, including PI3K-AKT and MAPKs. Reactive oxygen species (ROS) are intracellular molecules derived from the partial reduction of oxygen. ROS are highly reactive and govern cellular processes by their capacity to regulate signaling pathways (e.g., NF-κB, MAPKs, KEAP1-NRF2 and PI3K-AKT). Emerging evidence indicates that BMPs and ROS interplay in a number of ways. BMPs stimulate ROS production by inducing NOX expression, while ROS regulate the expression of several BMPs. Moreover, BMPs and ROS influence common signaling pathways, including PI3K/AKT and MAPK. Additionally, dysregulation of BMPs and ROS occurs in several pathologies, including vascular and musculoskeletal diseases, obesity, diabetes and kidney injury. Here, we review the current knowledge on the integration between BMP and ROS signals and its potential applications in the development of new therapeutic strategies.

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