scholarly journals Novel Toolboxes for the Investigation of Activity-Dependent Myelination in the Central Nervous System

2021 ◽  
Vol 15 ◽  
Author(s):  
Jack Kent Heflin ◽  
Wenjing Sun
Keyword(s):  
Cell Interaction ◽  
Precursor Cells ◽  
Signaling Cascades ◽  
Initial Contact ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Proliferation And Differentiation ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
Activity Dependent

Myelination is essential for signal processing within neural networks. Emerging data suggest that neuronal activity positively instructs myelin development and myelin adaptation during adulthood. However, the underlying mechanisms controlling activity-dependent myelination have not been fully elucidated. Myelination is a multi-step process that involves the proliferation and differentiation of oligodendrocyte precursor cells followed by the initial contact and ensheathment of axons by mature oligodendrocytes. Conventional end-point studies rarely capture the dynamic interaction between neurons and oligodendrocyte lineage cells spanning such a long temporal window. Given that such interactions and downstream signaling cascades are likely to occur within fine cellular processes of oligodendrocytes and their precursor cells, overcoming spatial resolution limitations represents another technical hurdle in the field. In this mini-review, we discuss how advanced genetic, cutting-edge imaging, and electrophysiological approaches enable us to investigate neuron-oligodendrocyte lineage cell interaction and myelination with both temporal and spatial precision.

scholarly journals Identification of a new regulation pathway of EGFR and E-cadherin dynamics

2020 ◽  
Author(s):  
Veronique Proux-Gillardeaux ◽  
Tamara Advedissian ◽  
Charlotte Perin ◽  
Jean-Christophe Gelly ◽  
Mireille Viguier ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Direct Interaction ◽  
Endocytic Pathway ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Epithelial Homeostasis ◽  
Proliferation And Differentiation ◽  
E Cadherin

ABSTRACTEGFR plays key roles in multiple cellular processes such as cell differentiation, cell proliferation, migration and epithelia homeostasis. Phosphorylation of the receptor, intracellular signaling and trafficking are major events regulating EGFR functions. Galectin-7, a soluble lectin expressed in epithelia such as the skin, has been shown to be involved in cell differentiation. Through this study we demonstrate that galectin-7 regulates EGFR function by a direct interaction with its extracellular domain hence modifying its downstream signaling and endocytic pathway. From observations in mice we focused on the molecular mechanisms deciphering the glycosylation dependent interaction between EGFR and galectin-7. Interestingly, we also revealed that galectin-7 is a direct binder of both EGFR and E-cadherin bridging them together. Strikingly this study not only deciphers a new molecular mechanism of EGFR regulation but also points out a novel molecular interaction between EGFR and E-cadherin, two major regulators of the balance between proliferation and differentiation.SUMMARYEGFR and E-cadherin are known to interact and to regulate epithelial homeostasis. In this study we unravel in the epidermis a new partner and regulator of EGFR which also binds E-cadherin reciprocally bridging their dynamics and functions.

scholarly journals Calcium Hypothesis of Gulf War Illness: Role of Calcium Ions in Neurological Morbidities in a DFP-Based Rat Model for Gulf War Illness

2020 ◽  
Vol 15 ◽  
pp. 263310552097984
Author(s):  
Kristin F Phillips ◽  
Laxmikant S Deshpande
Keyword(s):  
Experimental Models ◽  
Gulf War ◽  
Signaling Cascades ◽  
Gulf War Illness ◽  
Downstream Signaling ◽  
Cholinergic Signaling ◽  
Glutamatergic Signaling ◽  
The Central Nervous System ◽  
System Disorder

Gulf War Illness (GWI) refers to a multi-system disorder that afflicts approximately 30% of First Gulf War (GW) veterans. Amongst the symptoms exhibited, mood and memory impairment are commonly reported by GW veterans. Exposure to organophosphate (OP) compounds which target the cholinergic system is considered a leading cause for GWI symptoms. It is hypothesized that chronic OP-based war-time stimulation of cholinergic signaling led to recruitment of excitatory glutamatergic signaling and other downstream signaling cascades leading to neuronal injury, neuroinflammation, generation of reactive oxygen species, oxidative stress, and mitochondrial damage within the central nervous system. These findings have been observed in both experimental models and GWI veterans. In this context the role of calcium (Ca2+) signaling in GWI has come to the forefront. Here we present our Ca2+ hypothesis of GWI that suggests sustained neuronal Ca2+ elevations serve as a molecular trigger for pathological synaptic plasticity that has allowed for the persistence of GWI symptoms. Subsequently we discuss that therapeutic targeting of Ca2+ homeostatic mechanisms provides novel targets for effective treatment of GWI-related neurological signs in our rodent model.

scholarly journals TNFR2 Signaling Regulates the Immunomodulatory Function of Oligodendrocyte Precursor Cells

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1785
Author(s):  
Haritha L. Desu ◽  
Placido Illiano ◽  
James S. Choi ◽  
Maureen C. Ascona ◽  
Han Gao ◽  
...  
Keyword(s):  
Demyelinating Disease ◽  
Cell Interaction ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Proliferation And Differentiation ◽  
Progressive Neurodegeneration ◽  
Cytokine Tumor Necrosis Factor ◽  
Oligodendrocyte Precursor ◽  
Necrosis Factor

Multiple sclerosis (MS) is a neuroimmune disorder characterized by inflammation, CNS demyelination, and progressive neurodegeneration. Chronic MS patients exhibit impaired remyelination capacity, partly due to the changes that oligodendrocyte precursor cells (OPCs) undergo in response to the MS lesion environment. The cytokine tumor necrosis factor (TNF) is present in the MS-affected CNS and has been implicated in disease pathophysiology. Of the two active forms of TNF, transmembrane (tmTNF) and soluble (solTNF), tmTNF signals via TNFR2 mediating protective and reparative effects, including remyelination, whereas solTNF signals predominantly via TNFR1 promoting neurotoxicity. To better understand the mechanisms underlying repair failure in MS, we investigated the cellular responses of OPCs to inflammatory exposure and the specific role of TNFR2 signaling in their modulation. Following treatment of cultured OPCs with IFNγ, IL1β, and TNF, we observed, by RNA sequencing, marked inflammatory and immune activation of OPCs, accompanied by metabolic changes and dysregulation of their proliferation and differentiation programming. We also established the high likelihood of cell–cell interaction between OPCs and microglia in neuroinflammatory conditions, with OPCs able to produce chemokines that can recruit and activate microglia. Importantly, we showed that these functions are exacerbated when TNFR2 is ablated. Together, our data indicate that neuroinflammation leads OPCs to shift towards an immunomodulatory phenotype while diminishing their capacity to proliferate and differentiate, thus impairing their repair function. Furthermore, we demonstrated that TNFR2 plays a key role in this process, suggesting that boosting TNFR2 activation or its downstream signals could be an effective strategy to restore OPC reparative capacity in demyelinating disease.

Interpreting the mechanisms by which integrins promote the differentiation of mesenchymal stem cells and integrin application prospects

2021 ◽  
Vol 16 ◽  
Author(s):  
Liwei Ying ◽  
Chenggui Wang ◽  
Kesi Shi ◽  
Xiaopeng Zhou ◽  
Zhe Gong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Biological Activities ◽  
Signaling Cascades ◽  
Multilineage Differentiation ◽  
Integrin Receptors ◽  
Downstream Signaling ◽  
Current State ◽  
Proliferation And Differentiation ◽  
First Time

: Transmembrane integrin receptors represent a major composition of cell- extracellular matrix (ECM) communications that mediate cellular biological activities including proliferation and differentiation. Stem cells, especially mesenchymal stem cells (MSC) have rapidly emerged as promising therapies for various diseases. Dynamic links exist between extracellular and intracellular environments that profoundly influence the cellular activities via integrin receptors, such as cell morphology transformation and differentiation. Interpreting the roles of integrin receptors in the regulation of MSC differentiation may potentially lead to amplified therapeutic effect. In this review, we summarize, for the first time, the potential mechanisms by which integrins promote MSC multilineage differentiation including integrin downstream signaling cascades and the interactions between integrin and ion channels, the cytoskeleton and nuclear mechanoresponses. Furthermore, we focus on the current state and future prospects of the application of integrins to promote cell differentiation.

scholarly journals Perturbation of ubiquitin homeostasis promotes macrophage oxidative defenses

2018 ◽  
Author(s):  
Marie-Eve Charbonneau ◽  
Karla D. Passalacqua ◽  
Susan E. Hagen ◽  
Hollis D. Showalter ◽  
Christiane E. Wobus ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Specific Pattern ◽  
Innate Immune ◽  
Signaling Cascades ◽  
Innate Immune Responses ◽  
Post Translational Modification ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Phagocyte Nadph Oxidase ◽  
Protein Ubiquitination

Innate immune responses rely on specific pattern recognition receptors that induce downstream signaling cascades and promote inflammatory responses. Emerging evidence suggests that cells may also recognize alterations in cellular processes induced by infection. Protein ubiquitination is a post-translational modification essential for maintaining cellular homeostasis, and infection can cause global alterations in the host ubiquitin proteome. Here we used a chemical biology approach to perturb the cellular ubiquitin proteome as a simplified model to study the direct effect of ubiquitin homeostasis on macrophage responses. We show that perturbation of ubiquitin homeostasis results in a rapid and transient burst of reactive oxygen species (ROS) that promotes macrophage anti-infective capacity. ROS production was dependent on the activity of the phagocyte NADPH oxidase NOX2 and was associated with an increase in intracellular calcium. Our findings suggest that major changes in the host ubiquitin landscape may be a potent signal to rapidly deploy innate immune defenses.

Interrupting the FGF19-FGFR4 Axis to Therapeutically Disrupt Cancer Progression

2018 ◽  
Vol 19 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Liwei Lang ◽  
Austin Y. Shull ◽  
Yong Teng
Keyword(s):  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Tumor Development ◽  
Vital Role ◽  
Signaling Cascades ◽  
Cancer Cell Proliferation ◽  
Clinical Use ◽  
Fibroblast Growth ◽  
Apoptosis Resistance ◽  
Downstream Signaling

Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho has been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has been implicated in driving specific tumorigenic events including cancer cell proliferation, apoptosis resistance, and metastasis by activating a myriad of downstream signaling cascades. As an attractive target, several strategies implemented to disrupt the FGF19-FGFR4 axis have been developed in recent years, and FGF19-FGFR4 binding inhibitors are being intensely evaluated for their clinical use in treating FGF19-FGFR4 implicated cancers. Based on the established work, this review aims to detail how the FGF19-FGFR4 signaling pathway plays a vital role in cancer progression and why disrupting communication between FGF19 and FGFR4 serves as a promising therapeutic strategy for disrupting cancer progression.

scholarly journals The neuropathological impact of COVID-19: a review

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Ghadha Ibrahim Fouad
Keyword(s):  
Main Body ◽  
Respiratory Dysfunction ◽  
Behavior Understanding ◽  
Vital Functions ◽  
Global Issue ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
Neural Disorders ◽  
High Adaptation ◽  
Viral Outbreak

Abstract Background The Coronavirus disease 2019 (COVID-19) outbreak has become a challenging global issue after its emergence in December 2019. Due to the high adaptation of the virus, COVID-19 demonstrated a high transmission and infectivity potentials. Several studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induce deleterious neurological manifestations through interacting with the central nervous system (CNS). Main body The neuroinvasive potential of SARS-CoV-2 might contribute to its fatal behavior. Understanding the underlying mechanisms of this novel neuropathogen might contribute to the development of effective therapeutic strategies. The manifestations of neural damage in COVID-19 patients ranged from headache to severe encephalopathy and progression of preexisting neural disorders, it is speculated that neuroinvasion is strongly linked to the fatal respiratory dysfunction. The underlying neuropathological impact of emerging pneumonia (COVID-19) is still unclear. Conclusion This review demonstrated the urgent need to understand the neuropathology of COVID-19, to manage the current borderless viral outbreak of SARS-CoV-2 and its comorbidities. Moreover, SARS-CoV-2 could be regarded as an opportunistic neuropathogen that affects several vital functions in the human body.

Glycans in scaffold design in tissue reconstruction

2021 ◽  
pp. 088391152199784
Author(s):  
Nipun Jain ◽  
Shashi Singh
Keyword(s):  
Cell Attachment ◽  
Low Cost ◽  
Growth Conditions ◽  
Downstream Signaling ◽  
Cell Carrier ◽  
Wide Range ◽  
Proliferation And Differentiation ◽  
Different Types ◽  
Tissue Reconstruction ◽  
A Cell

Development of an artificial tissue by tissue engineering is witnessed to be one of the long lasting clarified solutions for the damaged tissue function restoration. To accomplish this, a scaffold is designed as a cell carrier in which the extracellular matrix (ECM) performs a prominent task of controlling the inoculated cell’s destiny. ECM composition, topography and mechanical properties lead to different types of interactions between cells and ECM components that trigger an assortment of cellular reactions via diverse sensing mechanisms and downstream signaling pathways. The polysaccharides in the form of proteoglycans and glycoproteins yield better outcomes when included in the designed matrices. Glycosaminoglycan (GAG) chains present on proteoglycans show a wide range of operations such as sequestering of critical effector morphogens which encourage proficient nutrient contribution toward the growing stem cells for their development and endurance. In this review we discuss how the glycosylation aspects are of considerable importance in everyday housekeeping functions of a cell especially when placed in a controlled environment under ideal growth conditions. Hydrogels made from these GAG chains have been used extensively as a resorbable material that mimics the natural ECM functions for an efficient control over cell attachment, permeability, viability, proliferation, and differentiation processes. Also the incorporation of non-mammalian polysaccharides can elicit specific receptor responses which authorize the creation of numerous vigorous frameworks while prolonging the low cost and immunogenicity of the substance.

scholarly journals Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 309
Author(s):  
Lijing Yang ◽  
Mengjia Hu ◽  
Yukai Lu ◽  
Songling Han ◽  
Junping Wang
Keyword(s):  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Inflammasome Activation ◽  
Hematopoietic Stem ◽  
Hematopoietic Transplantation ◽  
Proliferation And Differentiation ◽  
Extracellular Stimuli ◽  
Transplantation Complications ◽  
Underlying Mechanisms

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

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