Lipids and Cellular Membranes in Amyloid Diseases

Lipids and Cellular Membranes in Amyloid Diseases PDF Author: Raz Jelinek
Publisher: John Wiley & Sons
ISBN: 3527634339
Category : Science
Languages : en
Pages : 431

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Book Description
Addressing one of the biggest riddles in current molecular cell biology, this ground-breaking monograph builds the case for the crucial involvement of lipids and membranes in the formation of amyloid deposits. Tying together recent knowledge from in vitro and in vivo studes, and built on a sound biophysical and biochemical foundation, this overview brings the reader up to date with current models of the interplay between membranes and amyloid formation. Required reading for any researcher interested in amyloid formation and amyloid toxicity, and possible avenues for the prevention or treatment of neurodegenerative disorders. From the contents: * Interactions of Alpha-Synuclein with Lipids * Interaction of hIAPP and its Precursors with Membranes * Amyloid Polymorphisms: Structural Basis and Significance in Biology and Molecular Medicine * The Role of Lipid Rafts in Alzheimer's Disease * Alzheimer's Disease as a Membrane-Associated Enzymopathy of Beta-Amyloid Precursor Protein (APP) Secretases * Impaired Regulation of Glutamate Receptor Channels and Signaling Molecules by Beta-Amyloid in Alzheimer's Disease * Membrane Changes in BSE and Scrapie * Experimental Approaches and Technical Challenges for Studying Amyloid-Membrane Interactions and more

Lipids and Cellular Membranes in Amyloid Diseases

Lipids and Cellular Membranes in Amyloid Diseases PDF Author: Raz Jelinek
Publisher: John Wiley & Sons
ISBN: 3527634339
Category : Science
Languages : en
Pages : 431

Get Book Here

Book Description
Addressing one of the biggest riddles in current molecular cell biology, this ground-breaking monograph builds the case for the crucial involvement of lipids and membranes in the formation of amyloid deposits. Tying together recent knowledge from in vitro and in vivo studes, and built on a sound biophysical and biochemical foundation, this overview brings the reader up to date with current models of the interplay between membranes and amyloid formation. Required reading for any researcher interested in amyloid formation and amyloid toxicity, and possible avenues for the prevention or treatment of neurodegenerative disorders. From the contents: * Interactions of Alpha-Synuclein with Lipids * Interaction of hIAPP and its Precursors with Membranes * Amyloid Polymorphisms: Structural Basis and Significance in Biology and Molecular Medicine * The Role of Lipid Rafts in Alzheimer's Disease * Alzheimer's Disease as a Membrane-Associated Enzymopathy of Beta-Amyloid Precursor Protein (APP) Secretases * Impaired Regulation of Glutamate Receptor Channels and Signaling Molecules by Beta-Amyloid in Alzheimer's Disease * Membrane Changes in BSE and Scrapie * Experimental Approaches and Technical Challenges for Studying Amyloid-Membrane Interactions and more

The Importance of Macrophages, Lipid Membranes and Seeding in Experimental AA Amyloidosis

The Importance of Macrophages, Lipid Membranes and Seeding in Experimental AA Amyloidosis PDF Author: Aida Vahdat Shariatpanahi
Publisher: Linköping University Electronic Press
ISBN: 9176850501
Category :
Languages : en
Pages : 60

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Book Description
Amyloidosis is a group of protein misfolding diseases caused by tissue deposition of fibrillary protein aggregates termed amyloid. Amyloid A (AA) amyloidosis is a systemic form of amyloidosis that occurs as a complication of chronic inflammatory diseases, such as rheumatoid arthritis, familial Mediterranean fever and chronic infections, such as tuberculosis. AA amyloid is derived from the precursor protein serum amyloid A and is deposited in several organs preferably kidneys, liver and spleen. AA amyloidosis can be induced in mice by long standing inflammatory stimulation and concurrent administration of tissue extracts of AA amyloid, referred to as amyloid enhancing factor (AEF), reduces the time for amyloid deposition in the marginal zone of the spleen from 5 weeks to 2 days. The general aim of this thesis was to investigate the mechanisms involved in the development of AA amyloid in the mouse model of AA amyloidosis. Amyloid was induced in inflamed mice by injection of AEF and amyloid toxicity to splenic macrophages was investigated. We found that the marginal zone macrophages were very sensitive to amyloid formation and increasing amyloid load caused progressive depletion of these cells, whereas red pulp macrophages and metallophilic marginal zone macrophages appeared unaffected. To clarify the role of splenic macrophages in amyloidogenesis, macrophages were depleted by clodronate containing liposomes. We displayed that in the absence of splenic macrophages, especially marginal zone macrophages, amyloid formation was delayed implying a crucial role of macrophages in amyloid formation. The effect of lipid membranes on amyloid formation was studied and we showed that liposomes exhibited an amyloidogenic effect in inflamed mice although not as powerful as AEF. Following the fate of the liposomes, we showed that liposomes were rapidly cleared by uptake in the spleen and liver and colocalized with lysosomes. A tentative mechanism might be that accumulation of liposomes in lysosomes interfere with the SAA degradation process facilitating amyloid formation. Finally the conformational properties of two AEF (AEF1 and AEF2) preparations were studied using conformation sensitive luminescent-conjugated oligothiophenes (LCOs). We found that AEF1 and AEF2 displayed significantly different ultrastructure as well as conformation and consequently induced different cytotoxicity in vitro. Inducing amyloid formation in inflamed mice by AEF1 and AEF2 revealed that the polymorph of the amyloid aggregates was replicated in vivo. In summary, the results obtained in this thesis indicate an important role for macrophages for the formation of amyloid. The existence of amyloid strains has long been an in vitro finding, but the finding that AEF ultrastructure drives the morphology of newly formed amyloid in vivo opens up for new studies that can help us to understand the formation of homologous and heterologous fibrils. Thus, the fundamental mechanisms of various amyloid diseases are similar and the results presented in the thesis can increase the understanding of other amyloid diseases.

Membrane Lipid Signaling in Aging and Age-Related Disease

Membrane Lipid Signaling in Aging and Age-Related Disease PDF Author: M.P. Mattson
Publisher: Elsevier
ISBN: 0080522505
Category : Science
Languages : en
Pages : 237

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Book Description
The lipids of cellular membranes not only serve roles in controlling the structure and fluidity of the membrane, but are increasingly recognized for their roles as signalling molecules and modifiers of membrane protein function. Recent studies described in this volume reveal striking changes in membrane lipids during aging and in age-related diseases such as cancer, cardiovascular disease and neurodegenerative disorders. Lipids including inositol phospholipids, cholesterol, sphingolipids and ceramides play important roles in signalling cellular responses to stress and specific stimuli such as growth factors, cytokines and neurotransmitters. One or more of these lipid mediators has been linked to the pathogenesis of age-related diseases. This book provides a comprehensive review of specific membrane lipid mediators and their roles in aging and age-related disease.

Lipids in Protein Misfolding

Lipids in Protein Misfolding PDF Author: Olga Gursky
Publisher: Springer
ISBN: 3319173448
Category : Science
Languages : en
Pages : 270

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Book Description
​Protein conversion from a water-soluble native conformation to the insoluble aggregates and fibrils, which can deposit in amyloid plaques, underlies more than 20 human diseases, representing a major public health problem and a scientific challenge. Such a conversion is called protein misfolding. Protein misfolding can also involve errors in the topology of the folded proteins and their assembly in lipid membranes. Lipids are found in nearly all amyloid deposits in vivo, and can critically influence protein misfolding in vitro and in vivo in many different ways. This book focuses on recent advances in our understanding of the role of lipids in modulating the misfolding of various proteins. The main emphasis is on the basic biophysical studies that address molecular basis of protein misfolding and amyloid formation, and the role of lipids in this complex process.

Lipids in the Brain

Lipids in the Brain PDF Author: Elisabetta Albi
Publisher: Frontiers Media SA
ISBN: 288963986X
Category : Medical
Languages : en
Pages : 109

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Book Description
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Investigation of Amyloid-beta Peptide Interactions with Membrane Lipids

Investigation of Amyloid-beta Peptide Interactions with Membrane Lipids PDF Author: Martin Johan Olof Widenbrant
Publisher:
ISBN:
Category :
Languages : en
Pages : 380

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Book Description


Apolipoprotein E and Alzheimer’s Disease

Apolipoprotein E and Alzheimer’s Disease PDF 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.

The Neuropathology of Dementia

The Neuropathology of Dementia PDF Author: Margaret M. Esiri
Publisher: Cambridge University Press
ISBN: 9780521819152
Category : Medical
Languages : en
Pages : 600

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Book Description
Completely rewritten and updated, this new edition is almost twice the size of its predecessor. Illustrated in colour throughout, and with contributions from the world's leading authorities, it is the definitive reference on the neuropathology of dementia. It gives practical guidance to pathologists, describes the contribution of neuroimaging to diagnosis, and surveys the clinical features of dementia. New material includes: Three entirely new chapters on neuroimaging, molecular diagnostics, and transgenic models. Two chapters on tauopathies under new authorship. A chapter under new authorship on synucleinopathies, which includes multiple system atrophy.

Impact of Lipid Peroxidation on the Physiology and Pathophysiology of Cell Membranes

Impact of Lipid Peroxidation on the Physiology and Pathophysiology of Cell Membranes PDF Author: Angel Catalá
Publisher: Frontiers Media SA
ISBN: 2889450821
Category :
Languages : en
Pages : 90

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Book Description
The general process of lipid peroxidation consists of three stages: initiation, propagation, and termination. The initiation phase of lipid peroxidation includes hydrogen atom abstraction. Several species can abstract the first hydrogen atom and include the radicals: hydroxyl, alkoxyl, peroxyl, and possibly HO* 2. The membrane lipids, mainly phospholipids, containing polyunsaturated fatty acids are predominantly susceptible to peroxidation because abstraction from a methylene group of a hydrogen atom, which contains only one electron, leaves at the back an unpaired electron on the carbon. The initial reaction of *OH with polyunsaturated fatty acids produces a lipid radical (L*), which in turn reacts with molecular oxygen to form a lipid hydroperoxide (LOOH). Further, the LOOH formed can suffer reductive cleavage by reduced metals, such as Fe++, producing lipid alkoxyl radical (LO*). Peroxidation of lipids can disturb the assembly of the membrane, causing changes in fluidity and permeability, alterations of ion transport and inhibition of metabolic processes. In addition, LOOH can break down, frequently in the presence of reduced metals or ascorbate, to reactive aldehyde products, including malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), 4-hydroxy-2-hexenal (4-HHE) and acrolein. Lipid peroxidation is one of the major outcomes of free radical-mediated injury to tissue mainly because it can greatly alter the physicochemical properties of membrane lipid bilayers, resulting in severe cellular dysfunction. In addition, a variety of lipid by-products are produced as a consequence of lipid peroxidation, some of which can exert beneficial biological effects under normal physiological conditions. Intensive research performed over the last decades have also revealed that by-products of lipid peroxidation are also involved in cellular signalling and transduction pathways under physiological conditions, and regulate a variety of cellular functions, including normal aging. In the present collection of articles, both aspects (adverse and benefitial) of lipid peroxidation are illustrated in different biological paradigms. We expect this eBook may encourage readers to expand the current knowledge on the complexity of physiological and pathophysiological roles of lipid peroxidation.

Insights in Brain Disease Mechanisms: 2021

Insights in Brain Disease Mechanisms: 2021 PDF Author: Detlev Boison
Publisher: Frontiers Media SA
ISBN: 2832506658
Category : Science
Languages : en
Pages : 256

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Book Description