[PDF] Cellular Mechanisms Of Trafficking And Processing Of The Amyloid Precursor Protein App And Secretase Beta Secretase In Alzheimers Disease eBook

Author : C. Haass
Publisher : Karger Medical and Scientific Publishers
Page : 127 pages
File Size : 14,98 MB
Release : 2006-01-01
Category : Medical
ISBN : 3805581831

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This special topic issue of 'Neurodegenerative Diseases' contains contributions discussing the subject in-depth. 'Neurodegenerative Diseases' is a well-respected, international peer-reviewed journal in 'Neurobiology'. Special topic issues are included in the subscription.

Author : Fernando A. Oliveira
Publisher : Bentham Science Publishers
Page : 237 pages
File Size : 43,2 MB
Release : 2018-09-19
Category : Medical
ISBN : 1681087154

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Alzheimer’s Disease (AD) is the product of the slow and progressive degenerative alteration that develops in the adult brain and can remain asymptomatic for a considerable time before cognitive deficits becomes evident. The main challenge for researchers is to identify markers of this degenerative process, and, in this sense, data has been generated through experiments bringing to light new mechanisms and hypothesis to explain its pathophysiology. This book is a review of recent studies in AD molecular biology. Chapters explain various facets of AD, which include animal models, morphological changes, membrane composition, amyloidogenic peptides, intracellular transport systems, and the role of oxidative stress and calcium deregulation. Readers will understand the molecular mechanisms behind AD and therefore broaden their perspective on this neurodegenerative disease and its progression.

Author : Neurosciences Institute (New York, N.Y.)
Publisher : Wiley-Interscience
Page : 808 pages
File Size : 25,2 MB
Release : 1987
Category : Medical
ISBN :

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This book consists of five sections. The first section details methods for analyzing both presynaptic and postsynaptic function and emphasizes the molecular aspects of synapses. It describes ongoing studies of neurotransmitter release, voltage- sensitive ion channels, and electronic transmission at gap junctions. The second section focuses on the growing menagerie of neurotransmitters: their catagorization into chemical families, their relation to ion channels, their modulation by second messenger systems and their role in pharmacologic action. The third section considers the important relationship of transmitter diversity and synaptic types to the behavior of actual cellular networks. All of the studies described in these sections point to the necessity of considering interactions between anatomy, chemistry, physiology and pharmacology if synaptic function is to be understood at any one of these levels of analysis.

Author : Abel Lajtha
Publisher : Springer Science & Business Media
Page : 332 pages
File Size : 30,8 MB
Release : 2008-06-06
Category : Medical
ISBN : 0387326707

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The nervous system is highly fragile, especially during aging, illness and trauma. This book addresses a small sampling of major constituents of neural function at the cellular and molecular level that play crucial roles in development and aging.

Author : Ulrike C. Müller
Publisher : Frontiers Media SA
Page : 295 pages
File Size : 43,6 MB
Release : 2017-12-28
Category :
ISBN : 2889453553

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The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aβ peptide which is deposited in the brains of Alzheimer patients. Despite this, our knowledge of the normal cell biological and physiological functions of APP and the closely related APLPs is limited. This may have hampered our understanding of AD, since evidence has accumulated that not only the production of the Aβ peptide but also the loss of APP-mediated functions may contribute to AD pathogenesis. Thus, it appears timely and highly relevant to elucidate the functions of the APP gene family from the molecular level to their role in the intact organism, i.e. in the context of nervous system development, synapse formation and adult synapse function, as well as neural homeostasis and aging. Why is our understanding of the APP functions so limited? APP and the APLPs are multifunctional proteins that undergo complex proteolytical processing. They give rise to an almost bewildering array of different fragments that may each subserve specific functions. While Aβ is aggregation prone and neurotoxic, the large secreted ectodomain APPsα - produced in the non-amyloidogenic α-secretase pathway - has been shown to be neurotrophic, neuroprotective and relevant for synaptic plasticity, learning and memory. Recently, novel APP cleavage pathways and enzymes have been discovered that have gained much attention not only with respect to AD but also regarding their role in normal brain physiology. In addition to the various cleavage products, there is also solid evidence that APP family proteins mediate important functions as transmembrane cell surface molecules, most notably in synaptic adhesion and cell surface signaling. Elucidating in more detail the molecular mechanisms underlying these divers functions thus calls for an interdisciplinary approach ranging from the structural level to the analysis in model organisms. Thus, in this research topic of Frontiers we compile reviews and original studies, covering our current knowledge of the physiological functions of this intriguing and medically important protein family.

Author : J. Robin Harris
Publisher : Springer Science & Business Media
Page : 416 pages
File Size : 29,4 MB
Release : 2006-11-22
Category : Science
ISBN : 0387232265

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To understand Alzheimer's disease (AD) is one of the major thrusts of present-day clinical research, strongly supported by more fimdamental cellular, biochemical, immunological and structural studies. It is these latter that receive attention within this book. This compilation of 20 chapters indicates the diversity of work currently in progress and summarizes the current state of knowledge. Experienced authors who are scientifically active in their fields of study have been selected as contributors to this book, in an attempt to present a reasonably complete survey of the field. Inevitably, some exciting topics for one reason or another have not been included, for which we can only apologize. Standardization of terminology is often a problem in science, not least in the Alzheimer field; editorial effort has been made to achieve standardization between the Chapters, but some minor yet acceptable personal / author variation is still present, i. e. P-amyloid/amyloid-P; Ap42/Apl-42/APi. 42! The book commences with a broad survey of the contribution that the range of available microscopical techniques has made to the study of Alzheimer's amyloid plaques and amyloid fibrillogenesis. This chapter also serves as an Introduction to the book, since several of the topics introduced here are expanded upon in later chapters. Also, it is significant to the presence of this chapter that the initial discovery of brain plaques, by Alois Alzheimer, utilized light microscopy, a technique that continues to be extremely valuable in present-day AD research.

Author : Christopher Towlson
Publisher :
Page : 496 pages
File Size : 47,96 MB
Release : 2010
Category : Alzheimer's disease
ISBN :

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Alzheimer's disease (AD) brain pathology is characterised by the presence of senile plaques containing insoluble aggregates of the amyloid beta peptide (A[beta]). The mechanisms of A[beta] generation are not well understood but previous work has shown that amyloid precursor protein (APP) internalization from the cell surface may be an important step in this process. APP and the amyloidogenic enzymes involved in its processing have been shown to reside in cholesterol rich membrane micro-domains called lipid rafts. Lipid rafts are important cell signalling centres on the plasma membrane and may be involved in certain types of endocytosis. APP processing, including endocytosis, is also modulated by insulin signalling pathways. This thesis describes the generation and expression of APP endocytosis deficient mutants to study the role of APP intemalisation, insulin signalling and lipid rafts in A[beta] generation. -- Subcellular fractionation of cultured cells expressing human APP reveals that [beta]CTF, the direct precursor to A[beta], is found almost exclusively in lipid raft fractions. Furthermore, [beta]CTF is reduced in lipid rafts from cells expressing endocytosis deficient APP mutants. By contrast, APP endocytosis mutations have no effect on the localization of full-length APP or [beta]- and [gamma]-secretases. We also show that insulin treatment increases non-amyloidogenic processing of APP in neuroblastoma cells and primary mouse neurons, possibly by a mechanism involving decreased APP endocytosis. - Taken together, my results are consistent with the notion that plasma membrane bound APP and the [beta]-secretase BACE reside in distinct lipid raft species that merge upon endocytosis, resulting in enzyme and substrate converging in endosomes where APP is cleaved to generate A[beta]. Furthermore, altered APP endocytosis due to insulin resistance may increase the generation of A[beta] in AD.