scholarly journals The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-30 ◽  
Author(s):  
Giorgio Aquila ◽  
Luisa Marracino ◽  
Valeria Martino ◽  
Donato Calabria ◽  
Gianluca Campo ◽  
...  
Keyword(s):  
Notch Pathway ◽  
Cell Types ◽  
Inflammatory Disorder ◽  
Vascular Health ◽  
Current State ◽  
Notch Receptors ◽  
Prevention And Treatment ◽  
Potential Benefits ◽  
Prevention Of Atherosclerosis

Despite the currently available pharmacotherapies, today, thirty percent of worldwide deaths are due to cardiovascular diseases (CVDs), whose primary cause is atherosclerosis, an inflammatory disorder characterized by the buildup of lipid deposits on the inside of arteries. Multiple cellular signaling pathways have been shown to be involved in the processes underlying atherosclerosis, and evidence has been accumulating for the crucial role of Notch receptors in regulating the functions of the diverse cell types involved in atherosclerosis onset and progression. Several classes of nutraceuticals have potential benefits for the prevention and treatment of atherosclerosis and CVDs, some of which could in part be due to their ability to modulate the Notch pathway. In this review, we summarize the current state of knowledge on the role of Notch in vascular health and its modulation by nutraceuticals for the prevention of atherosclerosis and/or treatment of related CVDs.

scholarly journals Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen

2007 ◽  
Vol 204 (7) ◽  
pp. 1653-1664 ◽  
Author(s):  
Michele L. Caton ◽  
Matthew R. Smith-Raska ◽  
Boris Reizis
Keyword(s):  
Target Gene ◽  
Immune Cell ◽  
Notch Pathway ◽  
Cell Types ◽  
Innate Immune ◽  
Receptor Ligands ◽  
Notch Receptors ◽  
And Function

Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch–RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8− DC subset and reduced the frequency of cytokine-secreting CD8− DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J–deficient splenic CD8− DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8− DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch–RBP-J signaling controls the maintenance of CD8− DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.

The role of carotenoids in the prevention and treatment of cardiovascular disease – Current state of knowledge

2017 ◽  
Vol 38 ◽  
pp. 45-65 ◽  
Author(s):  
Bartosz Kulczyński ◽  
Anna Gramza-Michałowska ◽  
Joanna Kobus-Cisowska ◽  
Dominik Kmiecik
Keyword(s):  
Cardiovascular Disease ◽  
Current State ◽  
Prevention And Treatment

scholarly journals The Role of MicroRNAs in Repair Processes in Multiple Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1711 ◽  
Author(s):  
Conor P. Duffy ◽  
Claire E. McCoy
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Disorder ◽  
Cell Types ◽  
Repair Process ◽  
Rna Molecules ◽  
Current State ◽  
Non Coding Rna ◽  
Repair Mechanisms ◽  
Different Cell Types

Multiple sclerosis (MS) is an autoimmune disorder characterised by demyelination of central nervous system neurons with subsequent damage, cell death and disability. While mechanisms exist in the CNS to repair this damage, they are disrupted in MS and currently there are no treatments to address this deficit. In recent years, increasing attention has been paid to the influence of the small, non-coding RNA molecules, microRNAs (miRNAs), in autoimmune disorders, including MS. In this review, we examine the role of miRNAs in remyelination in the different cell types that contribute to MS. We focus on key miRNAs that have a central role in mediating the repair process, along with several more that play either secondary or inhibitory roles in one or more aspects. Finally, we consider the current state of miRNAs as therapeutic targets in MS, acknowledging current challenges and potential strategies to overcome them in developing effective novel therapeutics to enhance repair mechanisms in MS.

scholarly journals Notch Regulates Fibrocartilage Stem Cell Fate and Is Upregulated in Inflammatory TMJ Arthritis

2020 ◽  
Vol 99 (10) ◽  
pp. 1174-1181
Author(s):  
A. Ruscitto ◽  
V. Scarpa ◽  
M. Morel ◽  
S. Pylawka ◽  
C.J. Shawber ◽  
...  
Keyword(s):  
Cell Fate ◽  
Notch Pathway ◽  
Synovial Joint ◽  
Superficial Zone ◽  
Joint Injury ◽  
Stem Cell Fate ◽  
Notch Receptors ◽  
Tnf Α ◽  
Craniofacial Complex

The Notch pathway is critical for the development of the extracellular matrix in cartilage by regulating both anabolic and catabolic cellular activities. Similarly, Notch signaling plays a biphasic role in adult cartilage health and osteoarthritis by maintaining homeostasis and contributing to degeneration, respectively. The temporomandibular joint (TMJ) is the synovial joint of the craniofacial complex and is subject to injury and osteoarthritis. While Notch has been studied in axial skeletal joints, little is known about the role of Notch in TMJ development and disease. We identified fibrocartilage stem cells (FCSCs) localized within the TMJ condyle superficial zone niche that regenerate cartilage and repair joint injury. Here we investigate the role of Notch in regulating TMJ development and FCSC fate. Using a Notch reporter mouse, we discovered FCSCs localized within the TMJ superficial niche exhibit Notch activity during TMJ morphogenesis. We further showed that constitutively activating Notch promotes FCSC differentiation toward both cartilage and bone lineages, but inhibits adipogenesis. Using a TNF-α–induced TMJ inflammatory arthritis mouse model, we found that the expression of Notch receptors and ligands are upregulated and coupled with cells undergoing cartilage to bone transdifferentiation, which may contribute to TMJ pathogenesis. We also discovered that global Notch inhibition reduces osteogenic and chondrogenic differentiation of FCSCs. Together, these findings suggest that Notch is critical for FCSC fate specification and TMJ homeostasis, and reveal that inhibition of the Notch pathway may be a new therapeutic target for treating TMJ osteoarthritis.

scholarly journals Multifaceted regulation of Notch signaling by glycosylation

Glycobiology ◽  
2020 ◽  
Author(s):  
Ashutosh Pandey ◽  
Nima Niknejad ◽  
Hamed Jafar-Nejad
Keyword(s):  
Notch Signaling ◽  
Cell Biology ◽  
Normal Development ◽  
Notch Pathway ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Protein Glycosylation ◽  
Notch Receptors ◽  
Current Review ◽  
Notch Activation

Abstract To build a complex body composed of various cell types and tissues and to maintain tissue homeostasis in the postembryonic period, animals use a small number of highly conserved intercellular communication pathways. Among these is the Notch signaling pathway, which is mediated via the interaction of transmembrane Notch receptors and ligands usually expressed by neighboring cells. Maintaining optimal Notch pathway activity is essential for normal development, as evidenced by various human diseases caused by decreased and increased Notch signaling. It is therefore not surprising that multiple mechanisms are used to control the activation of this pathway in time and space. Over the last 20 years, protein glycosylation has been recognized as a major regulatory mechanism for Notch signaling. In this review, we will provide a summary of the various types of glycan that have been shown to modulate Notch signaling. Building on recent advances in the biochemistry, structural biology, cell biology and genetics of Notch receptors and the glycosyltransferases that modify them, we will provide a detailed discussion on how various steps during Notch activation are regulated by glycans. Our hope is that the current review article will stimulate additional research in the field of Notch glycobiology and will potentially be of benefit to investigators examining the contribution of glycosylation to other developmental processes.

Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2421-2432 ◽  
Author(s):  
M.H. Lin ◽  
C. Leimeister ◽  
M. Gessler ◽  
R. Kopan
Keyword(s):  
Transgenic Mice ◽  
Hair Follicle ◽  
Active Form ◽  
Notch Pathway ◽  
Dermal Papilla ◽  
Cell Types ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Hair Cortex

Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous effects are likely caused by cell-cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.

scholarly journals Oncogenic activation of the Notch1 gene by deletion of its promoter in Ikaros-deficient T-ALL

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5443-5454 ◽  
Author(s):  
Robin Jeannet ◽  
Jérôme Mastio ◽  
Alejandra Macias-Garcia ◽  
Attila Oravecz ◽  
Todd Ashworth ◽  
...  
Keyword(s):  
T Cell ◽  
Transcriptional Activation ◽  
Gene Deletion ◽  
Cell Transformation ◽  
Notch Pathway ◽  
Notch Receptors ◽  
Exon 1 ◽  
Specific Deletion

Abstract The Notch pathway is frequently activated in T-cell acute lymphoblastic leukemias (T-ALLs). Of the Notch receptors, Notch1 is a recurrent target of gain-of-function mutations and Notch3 is expressed in all T-ALLs, but it is currently unclear how these receptors contribute to T-cell transformation in vivo. We investigated the role of Notch1 and Notch3 in T-ALL progression by a genetic approach, in mice bearing a knockdown mutation in the Ikaros gene that spontaneously develop Notch-dependent T-ALL. While deletion of Notch3 has little effect, T cell–specific deletion of floxed Notch1 promoter/exon 1 sequences significantly accelerates leukemogenesis. Notch1-deleted tumors lack surface Notch1 but express γ-secretase–cleaved intracellular Notch1 proteins. In addition, these tumors accumulate high levels of truncated Notch1 transcripts that are caused by aberrant transcription from cryptic initiation sites in the 3′ part of the gene. Deletion of the floxed sequences directly reprograms the Notch1 locus to begin transcription from these 3′ promoters and is accompanied by an epigenetic reorganization of the Notch1 locus that is consistent with transcriptional activation. Further, spontaneous deletion of 5′ Notch1 sequences occurs in approximately 75% of Ikaros-deficient T-ALLs. These results reveal a novel mechanism for the oncogenic activation of the Notch1 gene after deletion of its main promoter.

The metalloprotease-disintegrin Kuzbanian participates in Notch activation during growth and patterning of Drosophila imaginal discs

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4769-4779 ◽  
Author(s):  
S. Sotillos ◽  
F. Roch ◽  
S. Campuzano
Keyword(s):  
Transmembrane Protein ◽  
Notch Pathway ◽  
Cell Types ◽  
Proteolytic Processing ◽  
Loss Of Function ◽  
Intercellular Signalling ◽  
Different Cell Types ◽  
Functional Receptor ◽  
Notch Activation

The Notch transmembrane protein is the receptor of an evolutionary conserved pathway that mediates intercellular signalling leading to the specification of different cell types during development. In this pathway, many aspects of the signal transduction mechanism remain poorly understood, especially the role of proteolytic processing of Notch. We present genetic evidence indicating that the metalloprotease-disintegrin kuzbanian (J. Rooke, D. Pan, T. Xu and G. M. Rubin (1996) Science 273, 1227–1231) is a new component of the Notch signalling pathway and is involved in Notch activation. kuzbanian genetic mosaics demonstrate that, during neurogenesis, wing margin formation and vein width specification kuzbanian is autonomously required in the cell where Notch is activated. Genetic interactions between kuzbanian and different genes of the Notch pathway indicate that kuzbanian is required upstream of Suppressor of Hairless. Moreover, the requirement of kuzbanian for signalling by a ligand-dependent Abruptex receptor, but not by a constitutively activated form of Notch, suggests that kuzbanian is involved in the generation of a Notch functional receptor and/or in its activation. However, differences in the phenotypes of loss-of-function Notch and kuzbanian mutations suggest the existence of alternative Kuzbanian-independent mechanisms that generate Notch functional receptors.

Directed Cellular Dynamics on Aligned STEP Fibrous Mechanistic Microenvironments

2011 ◽  
Author(s):  
Kevin Sheets ◽  
Amrinder Nain
Keyword(s):  
Cell Types ◽  
Polymeric Fibers ◽  
Exact Role ◽  
Cellular Behavior ◽  
Current State ◽  
Dry Spinning ◽  
Spatial Parameters ◽  
Different Cell Types

Cells attach to and interact with their immediate mechanistic native microenvironment. However, the current state-the-art in vitro cell studies are performed on flat substrates of glass, plastic or gel. [1]. The native environment consisting of an assembly of protein nanofibers forming the extracellular matrix (ECM) offers different mechanistic environments for different tissues, which elicits diverse cellular behavior [2]. Recently, there is increased interest in mimicking the ECM by depositing polymeric fibers in single and multiple layers using electrospinning, template synthesis, and micro dry-spinning. The key fibrous spatial parameters (diameter, alignment, spacing, and orientation) can be designed to generate microenvironments of varying mechanical properties. However, the exact role of these parameters on cellular behavior is not clearly understood. Hence, in this study we explore the topological-mechanistic effects of fibrous scaffolds on dynamics of different cell types.

scholarly journals Potential Role of Labisia pumila in the Prevention and Treatment of Chronic Diseases

2013 ◽  
Vol 2 (4) ◽  
pp. 55 ◽  
Author(s):  
Nik Hazlina Nik Hussain ◽  
Azidah Abdul Kadir
Keyword(s):  
Herbal Medicine ◽  
Postmenopausal Women ◽  
Chronic Diseases ◽  
Hormonal Therapy ◽  
Potential Role ◽  
East Asian ◽  
Prevention And Treatment ◽  
Potential Benefits ◽  
Labisia Pumila

<p><em>Labisia pumila</em> (Myrsinaceae), also called Kacip Fatimah, is a herbal medicine that has been widely used in South East Asian communities mainly for women’s health. The extensive use of this plant has led to many speculations and studies on its phytoestrogenic properties. This review highlights the studies that involved<em> Labisia pumila,</em> which include phytochemical profiling and its safety. In addition, we also look into its use as an alternative to hormonal therapy in postmenopausal women, and its role in cardiovascular protection and osteoporosis. Further studies are needed to highlight the potential benefits of this plant in promoting advantageous health properties. <em></em></p>

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