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Author: Roger Lefort Publisher: ISBN: Category : Languages : en Pages :
Book Description
We also found that dimerization of APP is sufficient to promote the amyloidogenic pathway, by increasing levels of the Î2-secretase BACE1, resulting in increased AÎ2 production. Finally, we found that dimerization of APP triggered caspase-dependent cleavage of APP and the formation of a second neurotoxic fragment, termed C31, which also mimics the effects of AÎ2 in hippocampal neurons. Taken together, our data provides support for the occurrence of a positive pathogenic feedback loop involving AÎ2, APP and C31 in neurons.
Author: Roger Lefort Publisher: ISBN: Category : Languages : en Pages :
Book Description
We also found that dimerization of APP is sufficient to promote the amyloidogenic pathway, by increasing levels of the Î2-secretase BACE1, resulting in increased AÎ2 production. Finally, we found that dimerization of APP triggered caspase-dependent cleavage of APP and the formation of a second neurotoxic fragment, termed C31, which also mimics the effects of AÎ2 in hippocampal neurons. Taken together, our data provides support for the occurrence of a positive pathogenic feedback loop involving AÎ2, APP and C31 in neurons.
Author: C.L. Masters Publisher: Springer Science & Business Media ISBN: 3662011352 Category : Science Languages : en Pages : 277
Book Description
This book summarizes the last ten years' research on Alzheimer's disease. Genetic mutations in the gene which codes for amyloid precursor protein (APP) have now been shown to cause Alzheimer's disease in some families. Other genetic loci are now being discovered which relate to Alzheimer's disease in some families. Understanding the normal structure and function of the APP gene product will eventually provide avenues for developing specific therapeutic strategies targeted at the amyloid deposition in the Alzheimer's disease brain. Drugs which can inhibit or dissolve the amyloid, affect the synthesis and proteolysis of APP, or which regulate the activity of the APP gene all hold the promise of eventually yielding an effective treatment for Alzheimer's disease.
Author: Ulrike C. Müller Publisher: Frontiers Media SA ISBN: 2889453553 Category : Languages : en Pages : 295
Book Description
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: Thimmaiah Govindaraju Publisher: Royal Society of Chemistry ISBN: 1839162732 Category : Medical Languages : en Pages : 694
Book Description
Alzheimer’s disease is an increasingly common form of dementia and despite rising interest in discovery of novel treatments and investigation into aetiology, there are no currently approved treatments that directly tackle the causes of the condition. Due to its multifactorial pathogenesis, current treatments are directed against symptoms and even precise diagnosis remains difficult as the majority of cases are diagnosed symptomatically and usually confirmed only by autopsy. Alzheimer’s Disease: Recent Findings in Pathophysiology, Diagnostic and Therapeutic Modalities provides a comprehensive overview from aetiology and neurochemistry to diagnosis, evaluation and management of Alzheimer's disease, and latest therapeutic approaches. Intended to provide an introduction to all aspects of the disease and latest developments, this book is ideal for students, postgraduates and researchers in neurochemistry, neurological drug discovery and Alzheimer’s disease.
Author: Weiming Xia Publisher: CRC Press ISBN: 0203492188 Category : Science Languages : en Pages : 240
Book Description
In the search for an effective treatment for Alzheimer's disease, APP is a unique model protein that illustrates the wide array of basic and sophisticated characterization techniques available. Exploring a variety of biological techniques to clarify the structure and function of this transmembrane protein, this text presents each method with detail
Author: Rudy Castellani Publisher: Biota Publishing ISBN: 1615047417 Category : Health & Fitness Languages : en Pages : 166
Book Description
Alzheimer’s Disease is characterized pathologically by two principal hallmark lesions: the senile plaque and the neurofibrillary tangle. Since the identification of each over 100 years ago, the major protein components have been elucidated. This has led in turn to the elaboration of metabolic cascades involving amyloid-β production in the case of the senile plaque, and phosphorylated-tau protein in the case of the neurofibrillary tangle. The pathogenesis and histogenesis of each have been the source of extensive investigation and some controversy in recent years, as both cascades have been implicated in the pathogenesis of Alzheimer’s Disease, relied upon in the diagnostic criteria for Alzheimer’s Disease at autopsy, and targeted for therapeutic intervention. With the accumulation of data and expansion of knowledge of the molecular biology of Alzheimer’s Disease, it appears that the enthusiasm for successful intervention has been premature. In this book, we detail the discovery and characterization of the major pathological lesions, their associated molecular biology, their relationship to clinical disease, and potential fundamental errors in understanding that may be leading scientific investigators in unintended directions.
Author: J. Robin Harris Publisher: Springer Science & Business Media ISBN: 0387232265 Category : Science Languages : en Pages : 416
Book Description
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: Roger Lefort
Author: Roger Lefort
Author: C.L. Masters
Author: Ulrike C. Müller
Author: Oliver Wilkes
Author: Elise Nguyen Le
Author: Thimmaiah Govindaraju
Author: James Daly
Author: Weiming Xia
Author: Rudy Castellani
Author: J. Robin Harris