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Destroying amyloid proteins with lasers
January 08, 2009
Researchers have found that a technique used to visualize amyloid fibers in the laboratory might have the potential to destroy them in the clinic. The technique involves zapping the fluorescently-tagged fibers with a laser, which can inhibit their growth and degrade them. This study, appearing in this week's JBC, may offer a non-drug alternative to treat amyloid-based disorders like Alzheimer, Parkinson, and Huntington diseases. Yuji Goto and colleagues had been studying amyloids, dense tangles of protein, to better understand how they form. In an effort to view amyloid formation under a microscope in real-time, they added an amyloid specific dye called thioflavin T (ThT) to the tangles and then hit it with a laser beam to induce fluorescence. Surprisingly, they found that under the right conditions, the laser could actually stop fiber growth and even degrade the amyloids. Goto and colleagues believe the laser-excited ThT transfers some of its energy to nearby oxygen, resulting in active oxygen species that alters the surrounding protein fibers. These specific experiments focused on beta2-microglobulin, a major component of amyloids associated with dialysis-related amyloidosis (a condition that currently has no good treatment), though they believe a similar approach of light-induced decomposition should work for other types of protein amyloids. American Society for Biochemistry and Molecular Biology

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The Functional Fold: Amyloid Structures in Nature
by Suzi Jarvis (Editor), Anika Mostaert (Editor)
Bringing together a wide variety of examples of functional amyloid in a single volume, this book explores the importance of amyloid fibrils in fungi, bacteria, algae, invertebrate, and vertebrate animals for providing environmental protection, structural integrity, and regulating biochemical processes. It highlights many of the extraordinary examples of functional amyloid found to date. It provides an exciting perspective for the study of amyloid deposits as important and useful protein structures widespread in nature.
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Amyloid and Related Disorders: Surgical Pathology and Clinical Correlations (Current Clinical Pathology)
by Maria M. Picken MD PhD FASN (Editor), Ahmet Dogan M.D. Ph.D. (Editor), Guillermo A. Herrera M.D. (Editor)
Abnormal proteins have been known to be associated with various pathologies. Most notably, these involve amyloidoses, monoclonal protein deposits associated with plasma cell dyscrasia/multiple myeloma, cryoglobulins and various related organized deposits. Systemic Amyloid and Related Disorders presents an overview of recent developments in the area including clinical presentation, etiology, pathogenesis, and differential diagnosis. The rationale for various therapies is also discussed. While the main portion of the text focuses on renal pathology, the involvement of other organ systems, such as cardiac, gastrointestinal and pulmonary pathology is also covered. This approach provides a unifying concept of these pathologic processes, which appear to have systemic involvement, and which...
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Lipids and Cellular Membranes in Amyloid Diseases
by Raz Jelinek (Editor)
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...
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Emerging Drugs and Targets for Alzheimer's Disease: Volume 1: Beta-Amyloid, Tau Protein and Glucose Metabolism (RSC Drug Discovery)
by Ana Martinez (Editor), David E Thurston (Editor)
Alzheimer's disease is the most prevalent neurodegenerative disorder in the elderly. A recent study from the Bloomberg School of Public Health recently estimated that over 26 million people were living with the disease in 2006 and that the global prevalence of the disease will grow to 106 million by 2050. By that time, 43 per cent of those living with the disease will need high-level care, equivalent to that of a nursing home. However, even if modest advances in preventing or delaying the disease's progression were made, it could have a huge impact on global public health. According to this study, interventions that could delay the onset of the disease by as little as one year would reduce the prevalence of the disease by 12 million fewer cases in 2050. These figures reinforce how...
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Amyloid Proteins: Methods and Protocols (Methods in Molecular Biology)
by Einar M. Sigurdsson (Editor), Miguel Calero (Editor), María Gasset (Editor)
Amyloid diseases are characterized by the deposition of insoluble fibrous amyloid proteins. The word “amyloid” indicates a starch-like compound, and though a misnomer, continues to be the accepted term for this group of protein conformational disorders. The second edition of Amyloid Proteins expands upon the previous edition with current, detailed protocols for the preparation of amyloid and its precursors, specific analytical methods for studying these proteins, cell culture models and assays for production of amyloid proteins, and protocols for amyloid extraction from tissue, its detection in vitro and in vivo, as well as nontransgenic methods for developing amyloid mouse models. Written in the highly successful Methods in Molecular Biology™ series format, chapters include...
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Alzheimer's Disease: Cellular and Molecular Aspects of Amyloid beta (Subcellular Biochemistry)
by Robin Harris (Editor), Falk Fahrenholz (Editor)
This book contains a survey of present-day research into the biomedical fundamentals of Alzheimer’s disease (AD). It contains 20 chapters dealing with widely ranging topics, all of which have a bearing upon the understanding and treatment of AD. Starting with a broad survey of the contribution that the various microscopical techniques (light microscopy, electron microscopy, atomic force microscopy) have made since the seminal light microscopical studies of Alois Alzheimer, the book presents chapters on specialist topics: transgenic mouse models of AD; the enzymology of amyloid-ß production and degradation; oxidant stress and antioxidant protection; the involvement of metal ions and the influence of chelators; the importance of amyloid-ß oligomers and fibrils, the role of cholesterol...
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Fibrous Proteins: Amyloids, Prions and Beta Proteins, Volume 73 (Advances in Protein Chemistry)
by John M. Squire (Author), David A.D. Parry (Author), Andrey Kajava (Author)
Amyloids, Prions and Beta Proteins is the last volume of the three-part thematic series on Fibrous Proteins in the Advances in Protein Chemistry serial. Fibrous proteins act as molecular scaffolds in cells providing the supporting structures of our skeletons, bones, tendons, cartilage, and skin. They define the mechanical properties of our internal hollow organs such as the intestines, heart, and blood vessels. This volume covers such topics as Beta-Structures in Fibrous Proteins; B-Silks: Enhancing and Controlling Aggregation; Beta-Rolls, Beta-Helices and Other Beta-Solenoid Proteins; Natural Triple B-Stranded Fibrous Folds; Structure, Function and Amyloidogenesis of Fungal Prions: Filament Polymorphism and Prion Variants; X-Ray Fiber and powder Diffraction of PRP Prion Peptides; From...
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Amyloid Proteins
by Jean D. Sipe (Editor)
A first-stop reference on proteins associated with amyloidosis. This book is the first to present a systematic overview of all known fibril-forming proteins, including their biochemical characteristics and pathophysiology. It considers the clinically recognized amyloid proteins that are known to be associated with the amyloid protein folding disorders, dealing with their common structural and thermodynamic features that lead to amyloid fibril formation and disease. Emphasis is on the thermodynamics of protein folding, the structure and physiologic effects of common oligomeric and subfibrillar intermediates and the influence of the extracellular matrix and cellular trafficking and metabolism on the genesis and catabolism of beta pleated sheet proteins. The chapters on specific...
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Amyloid, Prions, and Other Protein Aggregates, Part B, Volume 412 (Methods in Enzymology)
by Ronald Wetzel (Editor), Indu Kheterpal (Editor)
The ability of polypeptides to form alternatively folded, polymeric structures such as amyloids and related aggregates is being increasingly recognized as a major new frontier in protein research. This new volume of Methods in Enzymology along with Part C (volume 413) on Amyloid, Prions and other Protein Aggregates continue in the tradition of the first volume (309) in containing detailed protocols and methodological insights, provided by leaders in the field, into the latest methods for investigating the structures, mechanisms of formation, and biological activities of this important class of protein assemblies.
* Presents detailed protocols * Includes troubleshooting tips * Provides coverage on structural biology, computational...
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Amyloid, Prions, and Other Protein Aggregates, Part C, Volume 413 (Methods in Enzymology)
by Ronald Wetzel (Editor), Indu Kheterpal (Editor)
The ability of polypeptides to form alternatively folded, polymeric structures such as amyloids and related aggregates is being increasingly recognized as a major new frontier in protein research. This new volume of Methods in Enzymology along with Part B (volume 412) on Amyloid, Prions and other Protein Aggregates continue in the tradition of the first volume (309) in containing detailed protocols and methodological insights, provided by leaders in the field, into the latest methods for investigating the structures, mechanisms of formation, and biological activities of this important class of protein assemblies.
* Presents detailed protocols * Includes troubleshooting tips * Provides coverage on structural biology, computational...
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