protein phosphorylation in health and disease progress in molecular biology and translational science

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Protein Phosphorylation In Health And Disease

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ISBN : 9780123964809
Genre : Science
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This volume explores some of the most exciting recent advances in basic research on protein phosphorylation in health and disease and how this knowledge is leading to advances in the various fields. Contributions from leading authorities Informs and updates on all the latest developments in the field

Translational Control In Health And Disease

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ISBN : 008091196X
Genre : Science
File Size : 50. 98 MB
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Progress in Molecular Biology and Translational Science provides a forum for discussion of new discoveries, approaches, and ideas in molecular biology and translational science. It contains contributions from leaders in their fields and abundant references. This volume focuses on translational control in health and disease. * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

Metabotropic Gpcrs Tgr5 And P2y Receptors In Health And Diseases

Author : Senthilkumar Rajagopal
ISBN : 9789811315718
Genre : Medical
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This book will provide current understandings about two ubiquitously expressed metabotropic GPCRs, G-coupled purinoreceptor type 2 (P2Y) and Takeda G-protein-coupled bile acid receptor 5 (TGR5). G protein coupled receptors (GPCRs) are the largest family of proteins implicated in majority of cellular responses. The two receptor sub-families play a central role in many physiological functions as well as in many pathological conditions. This book offers up-to-date information on the physiological functions, signaling pathways and regulatory mechanisms of P2Y and TGR5 receptors. In addition, this book provides a comprehensive overview about the abnormalities of P2Y/TGR5 receptors and their contribution in the development and progression of pathological conditions. It also covers the currently available natural, chemical and pharmacological agents targeting these two receptor families and their therapeutic implications in P2Y and TGR5 associated disorders. This book is a valuable source for beginners and researchers to follow the rapidly progressing field of these two GPCR subfamily members.

Oligomerization In Health And Disease

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ISBN : 9780123869500
Genre : Science
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This special volume of Progress in Molecular Biology and Translational Science focuses on oligomerization in health and disease. Contributions from leading authorities Informs and updates on all the latest developments in the field

Investigating Mechanisms Of Angiogenesis In Health And Disease Using Zebrafish Models

Author : Zaheer Ali
ISBN : 9789176851999
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Angiogenesis, the growth of blood vessels from an existing vasculature, can occur by sprouting from preexisting vessels or by vessel splitting (intussusception). Pathological angiogenesis drives choroidal neovascularization (CNV) in age related macular degeneration (AMD) which is commonly restricted under the retinal pigment epithelium (RPE), called occult CNV, but may also involve vessels penetrating through the RPE into the sub-retinal space. Pathological vessels are poorly developed, insufficiently perfused and highly leaky, phenotypes that are considered to drive disease progression and lead to poor prognosis. Currently, a number of anti-angiogenic drugs exists, the majority of which target vascular endothelial factor (VEGF), but although they often are highly beneficial for treating eye diseases in the short-term, they are generally of limited efficacy in other diseases such as cancer, and also have poorer efficacy when used for treatment of eye diseases in the long-term. A better understanding of the mechanisms underlying pathological angiogenesis can generate new targets for treatment leading to development of better drugs for cancer and retinopathies, but perhaps also other angiogenesis-dependent diseases, in the future. In this thesis mechanisms involved in developmental angiogenesis or pathological angiogenesis in the choroid, cornea or melanoma was identified. These findings highlight the need to further elaborate our knowledge related to angiogenesis in different tissues/conditions for a more targeted, and potentially effective treatment of diseases in the future. In paper I, we for the first time identified the choriocapillaries (CCs) in adult zebrafish and found that occult CNV could be induced by exposing the fish to severe hypoxia. Interestingly, we found that occult CNV relied on intussusception, involving not only de novo generation of intussusceptive pillars but also a previously poorly understood mechanism called pillar splitting. This involved HIF-VEGF-VEGFR2 signaling and evidence that this also occurred in both rats and humans suffering from AMD suggested that the mechanism was conserved and clinically relevant. In contrast, we found in paper II that the development of CCs in the zebrafish relies on sprouting angiogenesis, involve continuous remodeling, and delayed maturation of the vasculature in 2D. The initial development was found to occur by a unique process of tissuewide synchronized vasculogenesis. As expected, VEGFA via VEGFR2 was also critical for the development of these vessels in the zebrafish embryo, but surprisingly this was independent on hypoxia-inducible factor (HIF)-1. Inflammatory nuclear factor-kB (NF-kB) signaling is involved in the progression of angiogenesis, but this signaling pathway has mainly been studied in the inflammatory cells and the role of NF-kB in the endothelial cells during angiogenesis is poorly understood. In paper III, we found that blocking NF-kB signaling using a specific IKK2 blocker IMD0354, specifically blocks pathological as well as developmental angiogenesis by targeting endothelial cell NF-kB signaling in the endothelial cells. Using a rat model for suture-induced corneal neovascularization, IMD0354 treatment lead to reduced production of inflammatory C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 5 (CXCL5) and VEGF, and thereby reduced pathological corneal angiogenesis in this model. Using the zebrafish tumor xenograft model in paper IV, we found an association between Microphthalmia associated transcription factor (MITF) and pigment epithelium derived factor (PEDF), which was involved in pathological tumor angiogenesis and metastasis. Similarly, in paper V we used zebrafish transplantation models to study and investigate the use of biocompatible polymers for the delivery of pro-angiogenic FGF-2 as a potential treatment strategy for ischemic diseases such as myocardial infarction (MI). Conclusively, this thesis provides new insights into diverse fields of angiogenic assays using zebrafish, and reveals new mechanisms of angiogenesis in health and disease. This work will hopefully provide a foundation for further studies into occult CNV related to AMD, a process that has not been possible to study previously in pre-clinical models. In addition, zebrafish xenograft or other transplantation models used in this work will likely be important to study cancer biology and to develop more attractive pharmaceutical preparations based on biocompatible hydrogels formulated as microspheres in the future.

G Protein Coupled Receptors In Health And Disease

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ISBN : 0080911943
Genre : Science
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G protein-coupled receptors (GPCRs) transduce signals from a diverse array of endogenous ligands, including ions, amino acids, nucleotides, lipids, peptides, and large glycoprotein hormones. They are also responsible for our sensing of exogenous stimuli, including photons and odorants. GPCRs regulate almost every aspect of our physiological functions. It is estimated that 40% to 50% of currently used therapeutic drugs target GPCRs directly or indirectly. Because the current drugs target only a small portion of the GPCRs, opportunities for targeting the remaining GPCRs is enormous. This volume reviews the latest developments in this rapidly advancing field. * This series provides a forum for discussion of new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

Progress In Molecular Biology And Translational Science

Author : Claude Bouchard
ISBN : UCLA:L0100620491
Genre : Molecular biology
File Size : 54. 49 MB
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Chronobiology Biological Timing In Health And Disease

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ISBN : 9780123972804
Genre : Science
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This special volume of Progress in Molecular Biology and Translational Science focuses on chronobiology. Contributions from leading authorities Informs and updates on all the latest developments in the field

Post Translational Modifications In Health And Disease

Author : Cecilio J. Vidal
ISBN : 1441963820
Genre : Science
File Size : 24. 82 MB
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Post-translational modifications serve many different purposes in several cellular processes such as gene expression, protein folding and transport to appropriate cell compartment, protein-lipid and protein-protein interactions, enzyme regulation, signal transduction, cell proliferation and differentiation, protein stability, recycling and degradation. Although several-hundred different modifications are known, the significance of many of them remains unknown. The enormous versatility of the modifications which frequently alter the physico-chemical properties of the respective proteins represents an extraordinary challenge in understanding their physiological role. Since essential cellular functions are regulated by protein modifications, an improvement of current understanding of their meaning might allow new avenues to prevent and/or alleviate human and animal diseases.

Protein Phosphorylation In Health And Disease

Author : Allegra Via
ISBN : 9782889199006
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File Size : 77. 91 MB
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Protein phosphorylation is one of the most abundant reversible post-translational modifications in eukaryotes. It is involved in virtually all cellular processes by regulating protein function, localization and stability and by mediating protein-protein interactions. Furthermore, aberrant protein phosphorylation is implicated in the onset and progression of human diseases such as cancer and neurodegenerative disorders. In the last years, tens of thousands of in vivo phosphorylation events have been identified by large-scale quantitative phospho-proteomics experiment suggesting that a large fraction of the proteome might be regulated by phosphorylation. This data explosion is increasingly enabling the development of computational approaches, often combined with experimental validation, aiming at prioritizing phosphosites and assessing their functional relevance. Some computational approaches also address the inference of specificity determinants of protein kinases/phosphatases and the identification of phosphoresidue recognition domains. In this context, several challenging issues are still open regarding phosphorylation, including a better understanding of the interplay between phosphorylation and allosteric regulation, agents and mechanisms disrupting or promoting abnormal phosphorylation in diseases, the identification and modulation of novel phosphorylation inhibitors, and so forth. Furthermore, the determinants of kinase and phosphatase recognition and binding specificity are still unknown in several cases, as well as the impact of disease mutations on phosphorylation-mediated signaling. The articles included in this Research Topic illustrate the very diverse aspects of phosphorylation, ranging from structural changes induced by phosphorylation to the peculiarities of phosphosite evolution. Some also provide a glimpse into the huge complexity of phosphorylation networks and pathways in health and disease, and underscore that a deeper knowledge of such processes is essential to identify disease biomarkers, on one hand, and design more effective therapeutic strategies, on the other.

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