Sierra Acai Company
Sierra Acai Company
Open 7 Days a Week
MonaVie Independent Distributor
Distributor Training
Shop Online
Enroll Now
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
Friends
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
07-SEPTEMBER-2008 03:17:44 - Amyloid For other uses, see Amyloid disambiguation. Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various other neurodegenerative diseases. Contents 1 Definition controversy 2 Diseases featuring amyloids 3 Non-disease amyloids 4 Amyloid biophysics 5 Amyloid pathology 6 Histological staining 7 References 8 External links Definition controversy The name amyloid comes from the early mistaken identification of the substance as starch amylum in Latin, based on crude iodine-staining techniques. For a period, the scientific community debated whether or not amyloid deposits were fatty deposits or carbohydrate deposits until it was finally resolved that it was neither, but rather a deposition of proteinaceous mass.1 The classical, histopathological definition of amyloid is an extracellular, proteinaceous deposit exhibiting beta sheet structure. This is due to mis-folding of unstable proteins. Common to most cross-beta type structures they are generally identified by apple-green birefringence when stained with congo red and seen under polarized light. These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes inhomogeneous structures.2 Recently this definition has come into question as some classic, amyloid species have been observed in distinctly intracellular locations. A more recent, biophysical definition is broader, including any polypeptide which adopts a cross-beta polymerization, in vivo, or in vitro. Some of these, although demonstrably cross-beta sheet, fail other characteristic tests of amyloid, such as the Congo red birefringence test. Microbiologists and biophysicists have largely adopted this definition, leading to some conflict in the biological community over an issue of language. The remainder of this article will be inclusive with due deference to the controversy by indicating where amyloid species are observed only in the biophysical context. Diseases featuring amyloids Medullary carcinoma of the thyroid Amyloidosis Alzheimer's disease Transmissible spongiform encephalopathy Type 2 diabetes mellitus Yeast Prions Sup35,3 Rnq1 Sporadic Inclusion Body Myositis S-IBM pheochromocytoma Osteomyelitis Non-disease amyloids mostly using the biophysical definition Native amyloids in organisms Curli E. coli Protein curlin Podospora Anserina Prion Het-s Malarial coat protein Spider silk some but not all spiders Mammalian melanosomes pMel Tissue-type plasminogen activator tPA, a hemodynamic factor Proteins and peptides known to make amyloid without any known disease Calcitonin Proteins and peptides engineered to make amyloid Amyloid biophysics Amyloid is characterized by a cross-beta sheet quaternary structure; that is, the beta-strands of the stacked beta-sheets come from different protein monomers and align perpendicular to the axis of the fibril. While amyloid is usually identified using fluorescent dyes, stain polarimetry, circular dichroism, or FTIR all indirect measurements, the gold-standard test to see if a structure contains cross-beta fibres is by placing a sample in an X-ray diffraction beam. There are two characteristic scattering diffraction signals produced at 4.7 and 10 Ã…ngstroms 0.47 nm and 1.0 nm, corresponding to the interstrand and stacking distances in beta sheets. It should be noted that the stacks of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built by aligned strands. Amyloid polymerization aggregation or non-covalent polymerization is generally sequence-sensitive, that is, causing mutations in the sequence can prevent self-assembly, especially if the mutation is a beta-sheet breaker, such as proline. For example, humans produce an amyloidogenic peptide associated with type II diabetes, but, in Rodentia, a proline is substituted in a critical location and amyloidogenesis does not occur. There are two broad classes of amyloid-forming polypeptide sequences. Glutamine-rich polypeptides are important in the amyloidogenesis of Yeast and mammalian prions, as well as Huntington's disease. When peptides are in a beta-sheet conformation, particularly when the residues are parallel and in-register causing alignment, glutamines can brace the structure by forming intrastrand hydrogen bonding between its amide carbonyls and nitrogens. In general, for this class of diseases, toxicity correlates with glutamine content. This has been observed in studies of onset age for Huntington's disease the longer the polyglutamine sequence, the sooner the symptoms appear, and has been confirmed in a C. elegans model system with engineered polyglutamine peptides. Other polypeptides and proteins such as amylin and the Alzheimer's beta protein do not have a simple consensus sequence and are thought to operate by hydrophobic association. Among the hydrophobic residues, aromatic amino-acids are found to have the highest amyloidogenic propensity. For these peptides, cross-polymerization fibrils of one polypeptide sequence causing other fibrils of another sequence to form is a phenomenon observed in vitro. This phenomenon is important since it would explain interspecies prion propagation and Amyloid biophysics differential rates of propagation, as well as a statistical link between Alzheimer's and diabetes. In general, cross-polymerization is more efficient the more similar the peptide sequence, though entirely dissimilar sequences can cross-polymerize and highly similar sequences can even be blockers which prevent polymerization. Polypeptides will not cross-polymerize their mirror-image counterparts, indicating that the phenomenon involves specific binding and recognition events. Xu, using atomic force microscopy, has shown in both lysozyme and human tau40 that formation of amyloid fibers is a two-step process in which proteins first aggregate into uniform colloidal spheres of ~20nm diameter.4 The spheres then join to form characteristic linear chains, which evolve over time into mature amyloid fibers. He proposes that colloidal aggregation drives conformational change and that a conformational change is not essential to initiate the aggregation process. Amyloid pathology The reasons for amyloid association with disease is unclear. In many cases, the deposits physically disrupt tissue architecture, suggesting disruption of function by some bulk process. In other cases, amyloid deposition precedes cell death, suggesting small amyloid-like oligomers possibly but not necessarily biophysically amyloid cause cell death. There is significant speculation that amyloid fibrils can also puncture cells or cause problems such as ionic imbalance in cells. Further speculation has led to the hypothesis that while amyloid association may be the cause of health issues, the association itself is initiated by an underlying problem, such as one/some of the above mentioned side effects like calcium ion concentration imbalances. Studies have shown that amyloid deposition is associated with mitochondrial dysfunction and a resulting generation of reactive oxygen species ROS, which can initiate a signaling pathway leading to apoptosis 5. Histological staining Clinically, amyloid diseases are typically identified by a change in the fluorescence intensity of planar aromatic dyes such as thioflavin T or congo red. Congo red positivity remains the gold standard for diagnosis of amyloidosis. This is generally attributed to the environmental change, as these dyes intercalate between beta-strands. Congophilic amyloid plaques generally cause apple-green birefringence, when viewed through crossed polarimetric filters. To avoid nonspecific staining, histology stains, such as hematoxylin and eosin stain, are used to quench the dyes' activity in other places where the dye might bind, such as the nucleus. Modern antibody technology and immunohistochemistry has made specific staining easier, but often this can cause trouble because epitopes can be concealed in the amyloid fold; an amyloid protein structure is generally a different conformation from that which the antibody recognizes. References ^ Kyle, R.A. 2001 Amyloidosis: a convoluted story. Brit. J. Haem. 114:529-538. PMID 11552976 ^ Sipe, J. D. and Cohen, A.S. 2000 Review: History of the Amyloid Fibril. J. Struct. Biol. 130:88-98. PMID 10940217 ^ Nakayashiki, PNAS, 2005 ^ Xu S. Aggregation drives misfolding in protein amyloid fiber formation. Amyloid 2007 Jun;142:119-31. PMID 17577685 ^ Kadowaki et al., 2005. Amyloid bold italic beta induces neuronal cell death through ROS-mediated ASK1 activation. Cell Death and Differentiation 12:19-24. 1 External links Amyloid Peptides at Bachem.com Amyloid Precursor Protein, CTF fragments at rpeptide.com Amyloid Treatment and Research Program at Boston University Amyloid: Journal of Protein Folding Disorders web page at tandf.co.uk Amyloidosis web page at Cornell University Information, support and advice to anyone with Amyloidosis, particularly in Australia www.amyloidosisaustralia.org Amyloidosis Support Network at amyloidosis.org UK National Amyloidosis Centre - one of the largest amyloid diagnosis and research centres at ucl.ac.uk Engineering Amyloid for material at University of California, Berkeley Amyloidosis Foundation amyloidosisresearchfoundation.org National Kidney and Urologic Diseases Information Clearinghouse at National Institute of Health Eubanks L, Rogers C, Beuscher A, Koob G, Olson A, Dickerson T, Janda K 2006. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol. Pharm. 3 6: 773-7. doi:10.1021/mp060066m. PMID 17140265. Amyloid Cascade Hypothesis v d e Metabolic disease: amyloidosis E85, 277.3 Forms of amyloid Serum amyloid P component - Serum amyloid A - Transthyretin - Beta-2 microglobulin - Bence Jones protein/Multiple myeloma - Amyloid precursor protein/Beta amyloid - Amylin Systemic amyloidosis AL amyloidosis - AA amyloidosis - Haemodialysis-associated amyloidosis - Senile systemic amyloidosis - Finnish type amyloidosis - Familial Merranean fever Organ-limited amyloidosis heart: Cardiac amyloidosis brain: Familial amyloid neuropathy - Cerebral amyloid angiopathy - Alzheimer's disease kidney: Familial renal amyloidosis cutaneous: Primary cutaneous amyloidosis Retrieved from http://en..org/wiki/Amyloid Categories: Metabolic disorders | Histopathology | Structural proteins Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Polski РуÑ?Ñ?кий Svenska ä¸æ–‡ This page was last modified on 24 August 2008, at 10:40
39 Reasons to Drink Acai Juice Every Day
What is MonaVie - Watch the 8-minute video
Discovering MonaVie Video
The Power of You Video
Effects of MonaVie Active on Antioxidant Capacity in Humans
Log into your Wholesale MonaVie Account
So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.