*  Lysozyme Amyloidogenesis Is Accelerated by Specific Nicking and Fragmentation but Decelerated by Intact Protein Binding and...
We have revisited the well-studied heat and acidic amyloid fibril formation pathway (pH 1.6, 65 °C) of hen egg-white lysozyme (HEWL) to map the barriers of the misfolding and amyloidogenesis pathways. A comprehensive kinetic mechanism is presented where all steps involving protein hydrolysis, fragmentation, assembly and conversion into amyloid fibrils are accounted for. Amyloid fibril formation of lysozyme has multiple kinetic barriers. First, HEWL unfolds within minutes, followed by irreversible steps of partial acid hydrolysis affording a large amount of nicked HEWL, the 49-101 amyloidogenic fragment and a variety of other species over 5-40 h. Fragmentation forming the 49-101 fragment is a requirement for efficient amyloid fibril formation, indicating that it forms the rate-determining nucleus. Nicked full-length HEWL is recruited efficiently into amyloid fibrils in the fibril growth phase ...
  http://liu.diva-portal.org/smash/record.jsf?pid=diva2:262849
*  Most recent papers with the keyword Som | Read by QxMD
Misfolded β-sheet structures of proteins leading to neurodegenerative diseases like Alzheimer's (AD) and Parkinson's diseases (PD) are in the spotlight since long. However, not much was known about the functional amyloids till the last decade. Researchers have become increasingly more concerned with the degree of involvement of these functional amyloids in human physiology. Interestingly, it has been found that the human body is exposed to a tremendous systemic amyloid burden, especially, during aging. Though many findings regarding these functional amyloids come up every day, some questions still remain unanswered like do these functional amyloids directly involve in the fibrillization of Amyloid beta (Aβ) 42 peptide or enhance the Aβ42 aggregation rate; whether functional bacterial amyloids (FuBA) co-localize with the senile plaques of AD or not ...
  https://www.readbyqxmd.com/keyword/33160
*  Amyloid formation may link Alzheimer disease and type 2 diabetes
Researchers first injected transgenic mice expressing human IAPP with preformed fibrils of synthetic IAPP, proIAPP, or beta-amyloid. After 10 months on a high-fat diet, tissue was analyzed using an amyloid-specific dye. The number of islets with amyloid was significantly increased compared to controls by all three types of fibrils, and the amyloid consisted of IAPP in all groups. No amyloid deposits were found in the spleen, kidney, liver, heart, or lungs. The results demonstrate for the first time that fibril injections could seed amyloid formation in the pancreas and also that brain amyloid could cross-seed fibril formation in the pancreas.. In subsequent experiments the investigators analyzed human tissues from the pancreas and brain. Using antibody-based methods, they found that pancreas sections with islet ...
  http://www.innovations-report.com/html/reports/medicine-health/amyloid-formation-may-link-alzheimer-disease-and-type-2-diabetes.html
*  More Evidence for Transthyretin Amyloid to Associate with Osteoarthritis - Fight Aging!
Amyloidosis is a protein conformational disorder in which amyloid fibrils accumulate in the extracellular space and induce organ dysfunction. Recently, two different amyloidogenic proteins, transthyretin (TTR) and apolipoprotein A-I (Apo A-I), were identified in amyloid deposits in knee joints in patients with knee osteoarthritis (OA). However, clinicopathological differences related to those two kinds of amyloid deposits in the knee joint remain to be clarified. Here, we investigated the clinicopathological features related to these knee amyloid deposits associated with knee OA and the biochemical characteristics of the amyloid deposits. We found that all of our patients with knee OA had amyloid deposits in the knee joints, especially in the meniscus, and those deposits were primarily derived from TTR and/or Apo A-I. Some patients with knee OA, however, had unclassified ...
  https://www.fightaging.org/archives/2016/10/more-evidence-for-transthyretin-amyloid-to-associate-with-osteoarthritis/
*  The Molecular Chaperone DNAJB6 - A Suppressor of Disease Related Amyloid Fibril Formation
phdthesis{f475f263-31b6-4989-81bd-1aa466807429, abstract = {Several neurodegenerative diseases are caused by peptides or proteins forming amyloid fibrils such as the Aβ peptide involved in Alzheimer's disease and the huntingtin exon-1 with a prolonged polyglutamine (polyQ) stretch involved in Huntington's disease. The ability to form amyloid fibrils is an intrinsic feature in all proteins. The fibrils are built up of monomers to form elongated structures with β-sheets perpendicular to the fiber axis. Molecular chaperones are involved in maintaining the protein homeostasis in the cells, in preventing protein aggregation, in refolding misfolded proteins and in mediating degradation of proteins and also in preventing amyloid fibril formation. DNAJB6 is a member of the HSP40 chaperone family, and has been found to be superior compared to other chaperones in its ability to prevent aggregation of huntingtin exon-1 in human cells. In this thesis we have expressed ...
  https://lup.lub.lu.se/search/publication/4779986
*  Localized amyloids important in diseases outside the brain : lessons from the islets of Langerhans and the thoracic aorta
It has long been understood that amyloids can be lethal in systemic diseases. More recently, it has been accepted that local cerebral aggregation of the small peptide A beta is involved in the pathogenesis of Alzheimer's disease. Protein aggregation, with the generation of small amyloid deposits in specific organs, also occurs outside the central nervous system and often is associated with increased cell death. In this review, we discuss two lesser known but common localized amyloid fibril-forming proteins: the polypeptide hormone islet amyloid polypeptide (IAPP) and the lactadherin-derived peptide medin. IAPP aggregates and induces the depletion of islet beta-cells in type 2 diabetes and in islets transplanted into type 1 diabetic subjects. Initial amyloid deposition occurs intracellularly and parts of this amyloid consist of proIAPP. Medin derived from ...
  http://uu.diva-portal.org/smash/record.jsf?pid=diva2:451533
*  British Library EThOS: The structure and physical properties of amyloid fibrils
Amyloid fibrils are associated with a range of highly debilitating neurological disorders including Alzheimer's disease, Parkinson's disease and the spongiform encephalopathies. These structures are formed by the misfolding and self-assembly of peptides and proteins varying widely in sequence and in native conformation. Here we combine experimental measurements derived from sold-state NMR, X-ray fibre diffraction and Atomic Force Microscopy to determine the complex, higher order protofilament structure adopted by an 11-amino acid peptide fragment of the human plasma protein transthyretin, TTR(105-115). This determination of the structure of amyloid fibrils to atomic resolution is crucial to the understanding of non-native protein self-assembly and the molecular basis of protein deposition diseases. We then demonstrate that amyloid fibrils, ordered supramolecular structures that we self-assemble from a wide range of polypeptide molecules, constitute a class ...
  http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599062
*  Protofibrillar Intermediates of Amyloid β-Protein Induce Acute Electrophysiological Changes and Progressive Neurotoxicity in...
In this study, we have compared the biological effects of different Aβ assemblies on primary mixed brain cultures to determine whether nonfibrillar or immature, prefibrillar forms of Aβ may be neurotoxic. This potentially important source of neuronal injury has been overlooked until very recently, perhaps because the neuropathological diagnosis of AD requires the presence of abundant fibrillar amyloid in the form of myriad neuritic plaques in postmortem brain tissue. Because mature amyloid plaques surrounded by dystrophic neurites, activated microglia, and reactive astrocytes are composed principally of Aβ fibrils, it has been generally assumed that fibrillar Aβ is the form most likely to be responsible for neuronal and glial injury in AD. The apparent importance of amyloid fibrils has been reinforced by cell culture studies that consistently show that the aggregation state of Aβ, most notably the formation of amyloid fibrils, is associated ...
  http://www.jneurosci.org/content/19/20/8876.long
*  Implications of Amyloid Pathology - Full Text View - ClinicalTrials.gov
There is compelling evidence supporting amyloid as one of the key pathologic agents in AD. Autopsy studies suggest the amount and location of fibrillar amyloid deposition does not relate strongly to the degree and type of clinical impairment, compared to tau pathology and neuronal loss. A substantial percentage of individuals known to be cognitively intact prior to death demonstrate significant amyloid pathology at autopsy. PIB-PET studies of older normal individuals have also demonstrated significant amyloid deposition in substantial percentages.. This study will test the hypothesis that amyloid is associated with synaptic dysfunction and neuronal damage. While some individuals are able to compensate for amyloid-related toxicity for an extended time period, sensitive imaging and neuropsychological markers will reveal that normal subjects with evidence of high amyloid burden do demonstrate ...
  https://clinicaltrials.gov/ct2/show/NCT00900770?term=alzheimer
*  Amyloid-Like Aggregates of the Yeast Prion Protein Ure2 Enter Vertebrate Cells by Specific Endocytotic Pathways and Induce...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
  http://pubmedcentralcanada.ca/pmcc/articles/PMC2932714/?lang=en-ca
*  amyloid
Actually, the photo depicts amyloid plaques, a frequent topic in the context of Alzheimer's disease. Pathologist William Lewis' photo reminds us that amyloid can also appear in the heart.. Amyloidosis of the heart is a set of complex diseases caused by the accumulation of cellular proteins that form an amyloid plaque. Although http://www.oakleyonorder.com/ amyloidosis was described more than 100 years ago, the causative proteins were not identified until recent chemical analyses were conducted. This image shows an amyloid plaque stained with Congo red stain and viewed through a polarized lens. The optical properties of the amyloid-forming protein cause it to appear green, while other matrix materials within the plaque appear as orange and blue.. The photo, which was one of the winners of the FASEB (Federation of American Societies for Experimental Biology) 2013 BioArt competition, was ...
  http://www.emoryhealthsciblog.com/tag/amyloid/
*  Two-photon absorption of polyfluorene aggregates stabilized by insulin amyloid fibrils - RSC Advances (RSC Publishing)
We report on the photophysical and optical properties of a polyfluorene derivative (PFO) and its binding to the amyloid-forming protein insulin. The complexation is based on weak supramolecular interactions between amyloid fibrils and PFO in dissolved and aggregated forms. In particular, complexes of polyflu
  http://pubs.rsc.org/en/Content/ArticleLanding/2015/RA/C5RA08302H
*  Fate of Cerebrospinal Fluid-Borne Amyloid β-Peptide: Rapid Clearance into Blood and Appreciable Accumulation by Cerebral...
Abstract: In Alzheimer's disease, the neuritic or senile amyloid plaques in hippocampus and association cortex, the diffuse plaques in brain areas such as the cerebellum and sensorimotor cortex, and the amyloid deposits in the walls of pial and parenchymal blood vessels are mainly composed of amyloid β-peptides. In the present study, either soluble 40-residue amyloid β-peptide radiolabeled with 125I (I-sAβ) or [14C]polyethylene glycol ([14C]-PEG, a reference material) was briefly infused into one lateral ventricle of normal rats. By 3.5 min, 30% of the I-sAβ was cleared from ventricular CSF into blood; another 30% was removed over the next 6.5 min. No [14C]PEG was lost from the CSF-brain system during the first 5 min, and only 20% was cleared by 10 min. Much of the I-sAβ that reached the subarachnoid space was retained by pial arteries and arterioles. Virtually no I-sAβ was found in brain. The clearance of amyloid β-peptides ...
  http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.1996.67020880.x/abstract
*  From hexamer to amyloid: marginal stability of apolipoprotein SAA2.2 leads to in vitro fibril formation at physiological...
Serum amyloid A (SAA) is a major acute phase reactant and a small apolipoprotein of high density lipoproteins (HDL) in the serum. In cases of prolonged inflammation, SAA may form amyloid fibrils, leading to the disease of amyloid A (AA) amyloidosis. Recently, we have shown that murine SAA2.2, a non-amyloidogenic isoform in vivo, forms a hexamer in vitro containing a putative central channel. It is reported herein that upon thermal denaturation, hexameric SAA2.2 irreversibly dissociates to a misfolded monomer at physiological temperature, formation of which coincides with a significant loss of alpha-helical and gain of beta-sheet structure. When SAA2.2 is incubated for several days at 37 degrees C, sedimentation analytical ultracentrifugation reveals the presence of soluble high molecular weight aggregates, which upon further incubation undergo subsequent self-assembly into amyloid fibrils. Limited ...
  https://infoscience.epfl.ch/record/142116
*  "Investigating the Modulation of Aggregating Amyloid Beta 40" by Marlee J. Motes
Amyloid beta protein has been linked to the formation of Alzheimer's disease in patients.¹ Plaques form from amyloid beta fibrils. The formation of these plaques between neural connections in the brain are associated with Alzheimer's disease.² The reduction of the formation of fibrils can be linked to utilizing protein mimics. The protocols that are used to reproduce the simulation of amyloid beta in the brain can be very important. Also, the structure of the protein mimic that is being used to inhibit the formation of fibrils can determine how the amyloid beta plaques are reduced.
  http://scholarworks.uark.edu/cheguht/91/
*  Amyloid Fibril Composition as a Predictor of Development of Cardiomyopathy After Liver Transplantation for Hereditary...
Background. Liver transplantation (LTx) is an accepted treatment for hereditary transthyretin (TTR) amyloidosis (ATTR). However, unforeseen heart complications, especially a rapid development of cardiomyopathy after LTx has affected mortality and morbidity. Recently, a relationship between ATTR-fibril composition and cardiomyopathy has been noted. The aim of this study was to investigate whether development of cardiomyopathy and heart failure in LTx ATTR amyloid patients is related to amyloid fibril composition.. Methods. Twenty-four patients with hereditary ATTR amyloidosis who had undergone LTx and have had their amyloid fibril type tested were available for the study. They had been examined by echocardiography including tissue Doppler and speckle tracking echocardiography before and after LTx. Patients were divided into two groups according to fibril composition, 10 patients with type A fibrils (a mixture of truncated and ...
  http://uu.diva-portal.org/smash/record.jsf?pid=diva2:542919
*  Alzheimer's-causing amyloid and bacteria trigger... UC Davis Health System Feature Story
Andreas Bäumler. The protein forming plaques in Alzheimer's patients is normally soluble. When the protein folds improperly, it forms amyloid deposits that are associated with brain inflammation. Until now, scientists have not been able to identify what causes this destructive, chronic inflammation.. Bäumler and his colleagues did not expect to be studying Alzheimer's disease. They were studying inflammation of the gut caused by bacteria when they discovered that the innate immune system was being triggered by a structural feature of bacterial amyloids and not by the amino acids that make up the proteins in the biofilms.. "When we destroyed the ability of the proteins to aggregate, we no longer saw the same immune response," Bäumler said.. When the researchers figured out the amyloid structure was responsible for triggering the immune system, they decided to see whether the same immune response was being triggered by structurally identical ...
  http://www.ucdmc.ucdavis.edu/welcome/features/20090909_Alzheimers/index.html
*  Amyloid purpura - wikidoc
The precise cause of amyloid purpura is unknown, but several mechanisms are thought to contribute.[2] One may be a decrease in the level of circulating factor X,[2] a clotting factor necessary for coagulation. The proposed mechanism for this decrease in factor X is that circulating amyloid fibrils bind and inactivate factor X.[2] Another contributing factor may be enhanced fibrinolysis,[2] the breakdown of clots. Subendothelial deposits of amyloid may weaken blood vessels and lead to the extravasation of blood.[2][3] Amyloid deposits in the gastrointestinal tract and liver may also play a role in the development of amyloid purpura.[2] ...
  http://wikidoc.org/index.php/Amyloid_purpura
*  Cannabinoid Effects on β Amyloid Fibril and Aggregate Formation, Neuronal and Microglial-Activated Neurotoxicity In Vitro
Cannabinoid (CB) ligands have demonstrated neuroprotective properties. In this study we compared the effects of a diverse set of CB ligands against β amyloid-mediated neuronal toxicity and activated microglial-conditioned media-based neurotoxicity in vitro, and compared this with a capacity to directly alter β amyloid (Aβ) fibril or aggregate formation. Neuroblastoma (SH-SY5Y) cells were exposed to Aβ1-42 directly or microglial (BV-2 cells) conditioned media activated with lipopolysaccharide (LPS) in the presence of the CB1 receptor-selective agonist ACEA, CB2 receptor-selective agonist JWH-015, phytocannabinoids Δ(9)-THC and cannabidiol (CBD), the endocannabinoids 2-arachidonoyl glycerol (2-AG) and anandamide or putative GPR18/GPR55 ligands O-1602 and abnormal-cannabidiol (Abn-CBD). TNF-α and nitrite production was measured in BV-2 cells to compare activation via LPS or albumin with Aβ1-42. Aβ1-42 evoked a concentration-dependent loss of cell viability in SH-SY5Y cells but ...
  http://uu.diva-portal.org/smash/record.jsf?pid=diva2:649280
*  Patent US5223482 - Recombinant Alzheimer's protease inhibitory amyloid protein and method of use - Google Patents
DNA sequences encoding β-amyloid-related proteins associated with Alzheimer's disease are disclosed. Also provided herein is a DNA sequence encoding a novel protease inhibitor. These sequences are used in producing or constructing recombinant β-amyloid core protein, β-amyloid-related proteins and recombinant or synthetic immunogenic peptides. Antibodies generated against the recombinant proteins or immunogenic peptides derived therefrom can be used for cerebral fluid or serum protein diagnosis of Alzheimer's disease.
  http://www.google.com/patents/US5223482?dq=oakley+5,387,949
*  Structure and Biomedical Applications of Amyloid Oligomer Nanoparticles
Amyloid oligomers are nonfibrillar polypeptide aggregates linked to diseases, such as Alzheimer's and Parkinson's. Here we show that these aggregates possess a compact, quasi-crystalline architect ...
  http://www.bionity.com/de/fachpublikationen/731150/structure-and-biomedical-applications-of-amyloid-oligomer-nanoparticles.html
*  The Culprit Is in the Cave : The Core Sites Explain the Binding Profiles of Amyloid-Specific Tracers
The design of molecular probes and tracer molecules with specificity toward amyloid beta (A beta) fibrils is of paramount importance for the selective diagnosis of Alzheimer's disease. This requires a detailed understanding of the binding sites in amyloid targets, their number, and their binding mechanism for various tracer molecules. We adopt an integrated approach including molecular docking, molecular dynamics, and generalized Born-based free energy calculations to investigate site-specific interactions of different amyloid binding molecules. Our study reproduces the experimental results on the relative binding affinity of the tracers and amyloid binders and explains the feature of "multiple binding sites" in amyloid targets as probed by competition binding experiments. A major outcome of this study is that it is the core sites of the Afi fibrils that are responsible for the experimentally reported binding profiles of ...
  http://uu.diva-portal.org/smash/record.jsf?pid=diva2:1010278
*  ALZFORUM | NETWORKING FOR A CURE
This is a beautiful paper that follows a large body of excellent work from these investigators. However, no data is presented as to how the disruption of the interaction between SAP and amyloid fibrils by their drug candidate affects the fate of the amyloid itself. This paper is focused exclusively on the clearance of SAP from the deposits. The authors state that they hope that the clearance of SAP will 'reduce the stability of amyloid deposits and promote their regression'. This is certainly a reasonable hypothesis, given that other studies have shown amyloid deposits can be cleared and that the SAP knockout mouse showed retarded and reduced disease.. However, it is very important to note that the systemic amyloidoses discussed in this paper seem to be caused by the amyloid fibrils themselves, whereas the neurodegenerative amyloidoses, including PD and AD, seem to be caused by a fibril ...
  http://www.alzforum.org/papers/amyloid-diseases-small-drugs-lead-attack
*  Chemistry: Faculty and Research
Neurofibrillary tangles (NFTs) are one of the two hallmark lesions of Alzheimer's disease (AD) and their accumulation has been used to assess the severity of the disease. They are composed of paired helical filaments (PHF), a form of amyloid resulting from the aggregation of the microtubule-associated protein tau. Our laboratory has found that peptides as short as 3-6 amino acids are able to initiate the formation of twisted filaments, similar to PHF. We believe that these short amyloid-forming peptides provide an excellent model for studying the structural basis of PHF and amyloid, in general. By understanding the structural basis for amyloid formation, a rational design of therapeutic agents able to prevent PHF accumulation can be undertaken. In addition to using short tau-related peptides to understand the basis of amyloid formation, they may be used as targeting agents for amyloid. For example, we have ...
  http://www.utdallas.edu/chemistry/faculty/
*  Kinetic theory of amyloid fibril templating
The growth of amyloid fibrils requires a disordered or partially unfolded protein to bind to the fibril and adapt the same conformation and alignment established by the fibril template. Since the H-bonds stabilizing the fibril are interchangeable, it is inevitable that H-bonds form between incorrect pairs of amino acids which are either incorporated into the fibril as defects or must be broken before the correct alignment can be found. This process is modeled by mapping the formation and breakage of H-bonds to a one-dimensional random walk. The resulting microscopic model of fibril growth is governed by two timescales: the diffusion time of the monomeric proteins, and the time required for incorrectly bound proteins to unbind from the fibril. The theory predicts that the Arrhenius behavior observed in experiments is due to off-pathway states rather than an on-pathway transition state. The predicted growth rates are in qualitative agreement with experiments on insulin fibril growth rates as a ...
  http://krex.k-state.edu/dspace/handle/2097/16213