Regulation of the Proteolytic Processing and Function of Amyloid Precursor Protein by Candidate Ligands PDF Download
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Author: Heather Caroline Rice
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Despite intense interest in the proteolysis of Amyloid Precursor Protein (APP) in Alzheimer's disease (AD), how the normal processing and function of this type I receptor-like glycoprotein is regulated remains ill-defined. APP is reported to function in neurodevelopment, including migration of neuronal precursor cells into the cortical plate. In recent years, several candidate ligands for APP, including F-spondin, Reelin, â1 Integrin, Contactins, and Lingo-1 have been reported. However, a cognate ligand for APP that regulates its function or processing has yet to be widely confirmed in multiple laboratories.
Author: Heather Caroline Rice
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Despite intense interest in the proteolysis of Amyloid Precursor Protein (APP) in Alzheimer's disease (AD), how the normal processing and function of this type I receptor-like glycoprotein is regulated remains ill-defined. APP is reported to function in neurodevelopment, including migration of neuronal precursor cells into the cortical plate. In recent years, several candidate ligands for APP, including F-spondin, Reelin, â1 Integrin, Contactins, and Lingo-1 have been reported. However, a cognate ligand for APP that regulates its function or processing has yet to be widely confirmed in multiple laboratories.
Author: Lauren Kristen Fong
Publisher:
ISBN:
Category :
Languages : en
Pages : 138
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Book Description
Successful development of effective therapeutics for Alzheimer's disease (AD) requires a deep understanding of the mechanisms of disease pathogenesis. Recent human induced pluripotent stem cell (hiPSC)-derived models have shown it is possible to recapitulate the complex genetic diversity of a patient and more completely model AD pathology. While most work has focused on neuronal AD phenotypes, there is mounting evidence that failure to regulate cholesterol homeostasis by neighboring nonneuronal support cells may be involved in AD pathogenesis. Amyloid precursor protein (APP) or multiple fragments generated by APP proteolytic processing have previously been implicated in the regulation of cholesterol metabolism. However, the physiological function of APP in regulating lipoprotein homeostasis in astrocytes, which are responsible for the brain's de novo cholesterol biosynthesis and regulation, remains unclear. To address this, we independently validated and characterized a novel in vitro differentiation protocol to generate human astrocytes from hiPSC. We found that cells derived by this method recapitulated native astrocytes in their form and function. We also utilized CRISPR/Cas9 genome editing to generate isogenic APP knockout (KO) hiPSCs. We found that APP KO astrocytes have reduced cholesterol, elevated levels of sterol regulatory element-binding protein (SREBP)-target gene transcripts, and increased low-density lipoprotein (LDL) receptor protein, all downstream consequences of reduced lipoprotein endocytosis. To elucidate which APP fragments regulate cholesterol homeostasis and examine whether familial AD mutations in APP affect lipoprotein metabolism, we analyzed an isogenic allelic series using the APP Swedish and APP V717F mutations. Only astrocytes homozygous for the APP Swedish (APPSwe/Swe) mutation, which had reduced full-length APP (FL APP) due to aggressive beta-secretase cleavage, recapitulated the APP KO phenotypes. Further, astrocytic internalization of amyloid-beta (A-beta), another ligand of LDL receptors, was impaired in APP KO and APPSwe/Swe astrocytes. Given that FL APP is known to bind to multiple LDL receptors, we propose that FL APP acts as a co-receptor for known LDL receptor ligands and is required for proper cholesterol homeostasis and A-beta clearance in human astrocytes.
Author: Astrid Sigel
Publisher: Wiley
ISBN: 9780470014882
Category : Science
Languages : en
Pages : 488
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Book Description
About the Series... Metal Ions in Life Sciences links coordination chemistry and biochemistry in their widest sense and thus increases our understanding of the relationship between the chemistry of metals and life processes. The series reflects the interdisciplinary nature of Biological Inorganic Chemistry and coordinates the efforts of scientists in fields like biochemistry, inorganic chemistry, coordination chemistry, molecular and structural biology, enzymology, environmental chemistry, physiology, toxicology, biophysics, pharmacy, and medicine. Consequently, the volumes are an essential source for researchers active in these and related fields as well as teachers preparing courses, e.g., in Bioinorganic Chemistry. About this Book... Volume 1, devoted solely to the vital research area concerning the role of metal ions in neurodegenerative diseases, offers in 15 stimulating chapters an authoritative and timely view of this fascinating subject. Written by 41 internationally recognized experts, Neurodegenerative Diseases and Metal Ions highlights, supported by 130 illustrations, the recent progress made in understanding the role metal ions play in diseases like transmissible spongiform encephalopathies (Creutzfeldt-Jakob and related diseases), Alzheimer's, Parkinson's, Huntington's, Wilson's and Menkes' diseases, as well as in familial amyotrophic lateral sclerosis and others. The interplay between metal ions, catecholamines and the formation of reactive oxygen species resulting in oxidative stress is considered, as is the metalloneurochemistry of zinc and the neurotoxicity of aluminum, cadmium, lead, and mercury. The need for novel drugs which manipulate metal-centered neuropathology is emphasized.
Author: Uday Kishore
Publisher: BoD – Books on Demand
ISBN: 9535110888
Category : Medical
Languages : en
Pages : 642
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Book Description
This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.
Author: Robert Vink
Publisher: University of Adelaide Press
ISBN: 0987073052
Category : Medical
Languages : en
Pages : 354
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Book Description
The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.
Author: Andrew Baird
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 542
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Book Description
Author:
Publisher: Academic Press
ISBN: 012816851X
Category : Science
Languages : en
Pages : 426
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Book Description
"Dancing protein clouds: Intrinsically disordered proteins in the norm and pathology" represents a set of selected studies on a variety of research topics related to intrinsically disordered proteins. Topics in this update include structural and functional characterization of several important intrinsically disordered proteins, such as 14-3-3 proteins and their partners, as well as proteins from muscle sarcomere; representation of intrinsic disorder-related concept of protein structure-function continuum; discussion of the role of intrinsic disorder in phenotypic switching; consideration of the role of intrinsically disordered proteins in the pathogenesis of neurodegenerative diseases and cancer; discussion of the roles of intrinsic disorder in functional amyloids; demonstration of the usefulness of the analysis of translational diffusion of unfolded and intrinsically disordered proteins; consideration of various computational tools for evaluation of functions of intrinsically disordered regions; and discussion of the role of shear stress in the amyloid formation of intrinsically disordered regions in the brain.
Author: A.D. Roses
Publisher: Springer Science & Business Media
ISBN: 3642801099
Category : Medical
Languages : en
Pages : 208
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Book Description
There is now considerable genetic evidence that the type 4 allele of the apolipoprotein E gene is a major susceptibility factor associated with late-onset Alzheimer's disease, the common form of the disease defined as starting after sixty years of age. The role of apolipoprotein E in normal brain metabolism and in the pathogenesis of Alzheimer's disease are new and exciting avenues of research. This book, written by the most outstanding scientists in this new filed, is the first presentation of results concerning the implications of apolipoprotein E on the genetics, cell biology, neuropathology, biochemistry, and therapeutic management of Alzheimer's disease.
Author: Nancy Y. Ip
Publisher: Springer Science & Business Media
ISBN: 0387788875
Category : Medical
Languages : en
Pages : 326
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Book Description
Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.
Author: Mikhail Soloviev
Publisher: John Wiley & Sons
ISBN: 0470196491
Category : Science
Languages : en
Pages : 432
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Book Description
The definitive guide to peptidomics- a hands-on lab reference The first truly comprehensive book about peptidomics for protein and peptide analysis, this reference provides a detailed description of the hows and whys of peptidomics and how the techniques have evolved. With chapters contributed by leading experts, it covers naturally occurring peptides, peptidomics methods and new developments, and the peptidomics approach to biomarker discovery. Explaining both the principles and the applications, Peptidomics: Methods and Applications: * Features examples of applications in diverse fields, including pharmaceutical science, toxicity biomarkers, and neuroscience * Details the successful peptidomic analyses of biological material ranging from plants to mammals * Describes a cross section of analytical techniques, including traditional methodologies, emerging trends, and new techniques for high throughput approaches An enlightening reference for experienced professionals, this book is sufficiently detailed to serve as a step-by-step guide for beginning researchers and an excellent resource for students taking biotechnology and proteomics courses. It is an invaluable reference for protein chemists and biochemists, professionals and researchers in drug and biopharmaceutical development, analytical and bioanalytical chemists, toxicologists, and others.
