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relating to or having the characteristics of a family; "children of the same familial background"; "familial aggregation"
occurring among members of a family usually by heredity; "an inherited disease"; "familial traits"; "genetically transmitted features" (同)genetic, hereditary, inherited, transmitted, transmissible

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家族の,家族特有の / 違伝的な,血統にあらわれる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/07/20 17:09:44」(JST)

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Micrograph showing amyloid deposits (pink) in small bowel. H&E stain.

Amyloids are aggregates of proteins that become folded into a shape that allows many copies of that protein to stick together forming fibrils. In the human body, amyloids may cause various diseases, as previously healthy proteins lose their normal physiological functions and form fibrous deposits in plaques around cells that disrupt the healthy function of tissues and organs. Such amyloids have been associated with more than 20 human diseases, known as amyloidosis, and may play a role in some neurodegenerative disorders.^[1] Some amyloid proteins are infectious; these are called prions in which the infectious form can act as a template to convert other non-infectious proteins into infectious form.^[2] Amyloids may also have normal biological functions; for example, in the formation of fimbriae in some genera of bacteria, transmission of epigenetic traits in fungi, as well as pigment deposition and hormone release in humans.^[3]

Amyloids have been known to arise from many different proteins and polypeptides.^[4] These polypeptide chains generally form β-sheet structures that aggregate into long fibers; however, identical polypeptides can fold into multiple distinct amyloid conformations. The diversity of the conformations may have led to different forms of the prion diseases.^[3]

Definition

The name amyloid comes from the early mistaken identification by Rudolf Virchow of the substance as starch (amylum in Latin, from Greek ἄμυλον amylon), based on crude iodine-staining techniques. For a period, the scientific community debated whether or not amyloid deposits are fatty deposits or carbohydrate deposits until it was finally found (in 1859) that they are, in fact, deposits of albumoid proteinaceous material.^[5]

Micrograph showing amyloid deposition in small bowel. Congo red stain.

The classical, histopathological definition of amyloid is an extracellular, proteinaceous deposit exhibiting beta sheet structure. Common to most cross-beta-type structures, in general, they are 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.^[6] Recently this definition has come into question as some classic, amyloid species have been observed in distinctly intracellular locations.^[7]
A more recent, biophysical definition is broader, including any polypeptide that polymerizes to form a cross-beta structure, in vivo or in vitro. Some of these, although demonstrably cross-beta sheet, do not show some classic histopathological characteristics such as the Congo-red birefringence. Microbiologists and biophysicists have largely adopted this definition,^[8]^[9] leading to some conflict in the biological community over an issue of language.

The remainder of this article will use the biophysical context.

Diseases featuring amyloids

Disease	Protein featured	Official abbreviation
Alzheimer's disease	Beta amyloid from Amyloid precursor protein^[10]^[11]^[12]^[13]	Aβ, APP
Diabetes mellitus type 2	IAPP (Amylin)^[14]^[15]	AIAPP
Parkinson's disease	Alpha-synuclein^[11]	none
Transmissible spongiform encephalopathy (e.g. bovine spongiform encephalopathy)	PrP^Sc^[16]	APrP
Fatal familial insomnia	PrP^Sc	APrP
Huntington's disease	Huntingtin^[17]^[18]	none
Medullary carcinoma of the thyroid	Calcitonin^[19]	ACal
Cardiac arrhythmias, isolated atrial amyloidosis	Atrial natriuretic factor	AANF
Atherosclerosis	Apolipoprotein AI	AApoA1
Rheumatoid arthritis	Serum amyloid A	AA
Aortic medial amyloid	Medin	AMed
Prolactinomas	Prolactin	APro
Familial amyloid polyneuropathy	Transthyretin	ATTR
Hereditary non-neuropathic systemic amyloidosis	Lysozyme	ALys
Dialysis related amyloidosis	Beta-2 microglobulin	Aβ2M
Finnish amyloidosis	Gelsolin	AGel
Lattice corneal dystrophy	Keratoepithelin	AKer
Cerebral amyloid angiopathy	Beta amyloid^[20]	Aβ
Cerebral amyloid angiopathy (Icelandic type)	Cystatin	ACys
Systemic AL amyloidosis	Immunoglobulin light chain AL^[19]	AL
Sporadic Inclusion body myositis	S-IBM	none

The International Society of Amyloidosis classifies amyloid fibrils based upon associated proteins.^[21]

Non-disease and functional amyloids

Native amyloids in organisms^[22]
- Curli fibrils produced by E. coli, Salmonella, and a few other members of the Enterobacteriales (Csg). The genetic elements (operons) encoding the curli system are phylogenetic widespread and can be found in at least four bacterial phyla.^[23] This suggest that many more bacteria may express curli fibrils.
- Gas vesicles, the buoyancy organelles of aquatic archaea and eubacteria^[24]
- Functional amyloids in Pseudomonas (Fap)^[25]^[26]
- Chaplins from Streptomyces coelicolor
- 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
- ApCPEB protein and its homologues with a glutamine-rich domain
- Peptide/protein hormones stored as amyloids within endocrine secretory granules^[27]
- Proteins and peptides engineered to make amyloid that display specific properties, such as ligands that target cell surface receptors^[28]
- Several yeast prions are based on an infectious amyloid, e.g. [PSI+] (Sup35p); [URE3] (Ure2p); [PIN+] (Rnq1p); [SWI1+] (Swi1p) and [OCT8+] (Cyc8p)
- Functional amyloids are abundant in most environmental biofilms according to staining with amyloid specific dyes and antibodies^[29]
- Fungal cell adhesion proteins aggregate on the surface of the fungi to form cell surface amyloid regions with greatly increased binding strength ^[30]^[31]
- The tubular sheaths encasing Methanosaeta thermophila filaments are the first functional amyloids to be reported from archeal domain of life ^[32]

"Amyloid deposits occur in the pancreas of patients with diabetes mellitus, although it is not known if this is functionally important. The major component of pancreatic amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or amylin. This is stored with insulin in secretory granules in B cells and is co secreted with insulin" (Rang and Dale's Pharmacology, 2015).

Amyloid biophysics

Structure

Amyloid is formed of long unbranched fibers that are characterized by a cross-beta sheet quaternary structure in which parallel chains of β-stranded peptides are arranged in an orientation perpendicular to the axis of the fiber. Each individual fiber may be 5–15 nanometres in width and a few micrometres in length.^[3] While amyloid is usually identified using fluorescent dyes, stain polarimetry, circular dichroism, or FTIR (all indirect measurements), the "gold-standard" test to see whether a structure contains cross-beta fibres is by placing a sample in an X-ray diffraction beam. The term "cross-beta" was based on the observation of two sets of diffraction lines, one longitudinal and one transverse, that form a characteristic "cross" pattern.^[33] There are two characteristic scattering diffraction signals produced at 4.7 and 10 Ångstroms (0.47 nm and 1.0 nm), corresponding to the interstrand and stacking distances in beta sheets.^[34] 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. The cross-beta pattern is considered a diagnostic hallmark of amyloid structure.^[3]

X-ray diffraction studies of microcrystals revealed atomistic details of core region of amyloid.^[35]^[36] The crystallographic structures show that short stretches from amyloid-prone regions of amyloidogenic proteins run perpendicular to the filament axis, confirming the "cross-beta" model. They also reveal a number of characteristics of amyloid structures – the two layers of beta-sheet are tightly packed together with the interface devoid of water (therefore referred to as dry interface), the opposing β-strands are slightly offset from each other, and their side-chains interdigitate with no hydrogen bond apart from those between stacks of asparagines and glutamines. The compact dehydrated interface created is termed steric-zipper interface.^[3] There are eight classes of steric-zipper interfaces, depending on types of beta-sheet (parallel and anti-parallel) and symmetry between two adjacent beta-sheets.

A variety of tertiary structures have been observed in amyloid. The β-sheets may form a β-sandwich, or a β-solenoid which may be either β-helix or β-roll. Identical polypeptides can fold into multiple distinct amyloid conformations.^[3]

Formation

Amyloid is formed through the polymerization of hundreds to thousands of monomeric peptides into long fibers. In general, amyloid polymerization (aggregation or non-covalent polymerization) is 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 or non-coded alpha-aminoisobutyric acid.^[37] For example, humans produce amylin, an amyloidogenic peptide associated with type II diabetes, but in rats and mice prolines are substituted in critical locations and amyloidogenesis does not occur.^{[citation needed]} Studies comparing synthetic to recombinant Amyloid beta 1-42 in assays measuring rate of fibrillation, fibril homogeneity, and cellular toxicity showed that recombinant Amyloid beta 1-42 has a faster fibrillation rate and greater toxicity than synthetic Amyloid beta 1-42 peptide.^[38] This observation combined with the irreproducibility of certain Amyloid beta 1-42 experimental studies has been suggested to be responsible for the lack of progress in Alzheimer's research.^[39] Consequently, there has been renewed efforts to manufacture Amyloid beta 1-42 and other amyloid peptides at unprecedented (>99%) purity.^[40]

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 Trinucleotide repeat disorders including Huntington's disease. When peptides are in a beta-sheet conformation, including arrangements in which the beta-strands are parallel and in-register (causing alignment of residues), glutamines can brace the structure by forming inter-strand hydrogen bonding between its amide carbonyls and nitrogens. In general, for this class of diseases, toxicity correlates with glutamine content.^{[citation needed]} 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.^[41]

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.^{[citation needed]} Among the hydrophobic residues, aromatic amino-acids are found to have the highest amyloidogenic propensity.^[42]^[43]

For these peptides, cross-polymerization (fibrils of one polypeptide sequence causing other fibrils of another sequence to form) is observed in vitro and possibly in vivo.^{[citation needed]} This phenomenon is important, since it would explain interspecies prion propagation and differential rates of prion propagation, as well as a statistical link between Alzheimer's and type 2 diabetes.^[44] In general, the more similar the peptide sequence the more efficient cross-polymerization is, though entirely dissimilar sequences can cross-polymerize and highly similar sequences can even be "blockers" that prevent polymerization.^{[citation needed]} Polypeptides will not cross-polymerize their mirror-image counterparts, indicating that the phenomenon involves specific binding and recognition events.^{[citation needed]}

The fast aggregation process, rapid conformational changes as well as solvent effects provide challenges in measuring monomeric and oligomeric amyloid peptide structures in solution. Theoretical and computational studies complement experiments and provide insights that are otherwise difficult to obtain using conventional experimental tools. Several groups have successfully studied the disordered structures of amyloid and reported random coil structures with specific structuring of monomeric and oligomeric amyloid as well as how genetics and oxidative stress impact the flexible structures of amyloid in solution.^[45]

Oligomeric intermediates of insulin during fibrillation (more toxic than other intermediates: native, protofibril, and fibril) decreased the surface tension of solution which indicated to detergent-like properties of oligomers and significant role of hydrophobic forces in cytotoxicity of oligomers.^[46]

Amyloid pathology

The reasons for amyloid association disease are unclear. In some cases, the deposits physically disrupt tissue architecture, suggesting disruption of function by some bulk process. An emerging consensus implicates prefibrillar intermediates rather than mature amyloid fibers in causing cell death.^[12]^[47]

Calcium dysregulation has been observed in cells exposed to amyloid oligomers. These small aggregates can form ion channels planar lipid bilayer membranes. Channel formation has been hypothesized to account for calcium dysregulation and mitochondrial dysfunction by allowing indiscriminate leakage of ions across cell membranes.^[48]

Studies have shown that amyloid deposition is associated with mitochondrial dysfunction and a resulting generation of reactive oxygen species (ROS), which can initiate a signalling pathway leading to apoptosis.^[49]

There are reports that indicate amyloid polymers (such as those of huntingtin, associated with Huntington's disease) can induce the polymerization of essential amyloidogenic proteins, which should be deleterious to cells. Also, interaction partners of these essential proteins can also be sequestered.^[50]

Histological staining

In the clinical setting, amyloid diseases are typically identified by a change in the fluorescence intensity of planar aromatic dyes such as thioflavin T, congo red or NIAD-4.^[51] In general, this is attributed to the environmental change, as these dyes intercalate between beta-strands to confine their structure.^[52] Congo Red positivity remains the gold standard for diagnosis of amyloidosis. In general, binding of Congo Red to amyloid plaques produces a typical apple-green birefringence when viewed under cross-polarized light. To avoid nonspecific staining, other histology stains, such as the hematoxylin and eosin stain, are used to quench the dyes' activity in other places such as the nucleus, where the dye might bind. 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; in general, an amyloid protein structure is a different conformation from the one that the antibody recognizes.

References

^ Pulawski, W; Ghoshdastider, U; Andrisano, V; Filipek, S (2012). "Ubiquitous amyloids". Applied Biochemistry and Biotechnology. 166 (7): 1626–43. PMC 3324686 . PMID 22350870. doi:10.1007/s12010-012-9549-3.
^ Claudio Soto, Lisbell Estrada, Joaquín Castilla (March 2006). "Amyloids, prions and the inherent infectious nature of misfolded protein aggregates". Trends in Biochmical Science. 31 (3): 150–5. PMID 16473510. doi:10.1016/j.tibs.2006.01.002.
^ ^a ^b ^c ^d ^e ^f Brandon H. Toyama and Jonathan S. Weissman (2011). "Amyloid Structure: Conformational Diversity and Consequences". Annual Review of Biochemistry. 80: 557–85. PMC 3817101 . PMID 21456964. doi:10.1146/annurev-biochem-090908-120656.
^ Marina Rami´rez-Alvarado; Jane S. Merkel & Lynne Regan (2000). "A systematic exploration of the influence of the protein stability on amyloid fibril formation in vitro". PNAS. 97 (16): 8979–84. PMC 16807 . PMID 10908649. doi:10.1073/pnas.150091797.
^ Kyle R.A. (2001). "Amyloidosis: a convoluted story". Brit. J. Haem. 114 (3): 529–38. PMID 11552976. doi:10.1046/j.1365-2141.2001.02999.x.
^ Sipe J. D.; Cohen A.S. (2000). "Review: History of the Amyloid Fibril". J. Struct. Biol. 130 (2–3): 88–98. PMID 10940217. doi:10.1006/jsbi.2000.4221.
^ Lin CY, Gurlo T, Kayed R, et al. (May 2007). "Toxic human islet amyloid polypeptide (h-IAPP) oligomers are intracellular, and vaccination to induce anti-toxic oligomer antibodies does not prevent h-IAPP-induced beta-cell apoptosis in h-IAPP transgenic mice". Diabetes. 56 (5): 1324–32. PMID 17353506. doi:10.2337/db06-1579.
^ Nilsson MR (September 2004). "Techniques to study amyloid fibril formation in vitro". Methods (San Diego, Calif.). 34 (1): 151–60. PMID 15283924. doi:10.1016/j.ymeth.2004.03.012.
^ Fändrich M (August 2007). "On the structural definition of amyloid fibrils and other polypeptide aggregates". Cellular and molecular life sciences : CMLS. 64 (16): 2066–78. PMID 17530168. doi:10.1007/s00018-007-7110-2.
^ Chiang PK, Lam MA, Luo Y (September 2008). "The many faces of amyloid beta in Alzheimer's disease". Current molecular medicine. 8 (6): 580–04. PMID 18781964. doi:10.2174/156652408785747951. Archived from the original on 2011-10-06.
^ ^a ^b Irvine GB, El-Agnaf OM, Shankar GM, Walsh DM (2008). "Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases". Molecular medicine (Cambridge, Mass.). 14 (7–8): 451–64. PMC 2274891 . PMID 18368143. doi:10.2119/2007-00100.Irvine.
^ ^a ^b Ferreira ST, Vieira MN, De Felice FG (2007). "Soluble protein oligomers as emerging toxins in Alzheimer's and other amyloid diseases". IUBMB Life. 59 (4–5): 332–45. PMID 17505973. doi:10.1080/15216540701283882.
^ Hamley IW (2012). "The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization". Chemical Reviews. 112: 5147–5192. PMID 22813427. doi:10.1021/cr3000994.
^ Haataja L, Gurlo T, Huang CJ, Butler PC (May 2008). "Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis". Endocrine Reviews. 29 (3): 303–16. PMC 2528855 . PMID 18314421. doi:10.1210/er.2007-0037.
^ Höppener JW, Ahrén B, Lips CJ (August 2000). "Islet amyloid and type 2 diabetes mellitus". The New England Journal of Medicine. 343 (6): 411–19. PMID 10933741. doi:10.1056/NEJM200008103430607.
^ "More than just mad cow disease". Nature Structural Biology. 8 (4): 281. 2001. doi:10.1038/86132.
^ Truant R, Atwal RS, Desmond C, Munsie L, Tran T (September 2008). "Huntington's disease: revisiting the aggregation hypothesis in polyglutamine neurodegenerative diseases". The FEBS Journal. 275 (17): 4252–62. PMID 18637947. doi:10.1111/j.1742-4658.2008.06561.x.
^ Weydt P, La Spada AR (August 2006). "Targeting protein aggregation in neurodegeneration – lessons from polyglutamine disorders". Expert opinion on therapeutic targets. 10 (4): 505–13. PMID 16848688. doi:10.1517/14728222.10.4.505.
^ ^a ^b "Amyloidosis, Overview" by Bruce A Baethge and Daniel R Jacobson
^ Dotti CG, De Strooper B (February 2009). "Alzheimer's dementia by circulation disorders: when trees hide the forest". Nat. Cell Biol. 11 (2): 114–16. PMID 19188916. doi:10.1038/ncb0209-114.
^ Sipe JD, Benson MD, Buxbaum JN, et al. (September 2010). "Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis". Amyloid. 17 (3–4): 101–04. PMID 21039326. doi:10.3109/13506129.2010.526812.
^ Hammer ND, Wang X, McGuffie BA, Chapman MR (May 2008). "Amyloids: friend or foe?". Journal of Alzheimer's disease : JAD. 13 (4): 407–19. PMC 2674399 . PMID 18487849. ^{[permanent dead link]}
^ Dueholm M. S.; Albertsen M.; Otzen D.; Nielsen P. H. (2012). Webber, Mark Alexander, ed. "Curli functional amyloid systems are phylogenetically widespread and display large diversity in operon and protein structure". PLOS ONE. 7 (12): e51274. PMC 3521004 . PMID 23251478. doi:10.1371/journal.pone.0051274.
^ Bayro, Marvin J.; Daviso, Eugenio; Belenky, Marina; Griffin, Robert G.; Herzfeld, Judith (2012). "An Amyloid Organelle, Solid-state NMR Evidence for Cross-beta Assembly of Gas Vesicles". The Journal of Biological Chemistry. 287 (5): 3479–84. PMC 3271001 . PMID 22147705. doi:10.1074/jbc.M111.313049.
^ Dueholm M. S.; Petersen S. V.; Sønderkaer M.; Larsen P.; Christiansen G.; Hein K. L.; Enghild J. J.; Nielsen J. L.; Nielsen K. L.; Nielsen P. H.; Otzen D. E. (2010). "Functional amyloid in Pseudomonas". Mol Microbiol. 77 (4): 1009–20. PMID 20572935. doi:10.1111/j.1365-2958.2010.07269.x.
^ Dueholm M. S.; Søndergaard M. T.; Nilsson M.; Christiansen G.; Stensballe A.; Overgaard M. T.; Givskov M.; Tolker-Nielsen T.; Otzen D. E.; Nielsen P. H. (2013). "Expression of Fap amyloids in Pseudomonas aeruginosa, P. fluorescens, and P. putida results in aggregation and increased biofilm formation". Microbiologyopen. 2 (3): 365–82. PMC 3684753 . PMID 23504942. doi:10.1002/mbo3.81.
^ Maji, S.K.; et al. (2009). "Functional Amyloids As Natural Storage of Peptide Hormones in Pituitary Secretory Granules". Science. 325 (5938): 328–32. PMC 2865899 . PMID 19541956. doi:10.1126/science.1173155.
^ Bongiovanni, M.N.; et al. (2011). "Functional fibrils derived from the peptide TTR1-cycloRGDfK that target cell adhesion and spreading". Biomaterials. 32 (26): 6099–110. PMID 21636126. doi:10.1016/j.biomaterials.2011.05.021.
^ Larsen P.; Nielsen J. L.; Dueholm M. S.; Wetzel R.; Otzen D.; Nielsen P. H. (2007). "Amyloid adhesins are abundant in natural biofilms". Environ Microbiol. 9 (12): 3077–90. PMID 17991035. doi:10.1111/j.1462-2920.2007.01418.x.
^ Garcia M.C.; Lee J.T.; Ramsook C.B; Alsteens D.; Dufrene Y.F; Lipke P.N. (2011). "A role for amyloid in cell aggregation and biofilm formation". PLOS ONE. 6: e17632. PMC 3050909 . PMID 21408122. doi:10.1371/journal.pone.0017632.
^ Lipke P.N.; Garcia M.C.; Alsteens D.; Ramsook C.B.; Klotz S.A.; Dufrêne Y.F. (2012). "Strengthening relationships: amyloids create adhesion nanodomains in yeasts". Trends Microbiol. 20: 59–65. PMC 3278544 . PMID 22099004. doi:10.1016/j.tim.2011.10.002.
^ Dueholm, M.S.; et al. (2015). "The Tubular Sheaths Encasing Methanosaeta thermophila Filaments are Functional Amyloids". J Biol Chem. 290: jbc.M115.654780. PMC 4536462 . PMID 26109065. doi:10.1074/jbc.M115.654780.
^ Wormell RL. New fibres from proteins. Academic Press, 1954, p. 106.
^ Sunde M.; Serpell L. C.; et al. (1997). "Common core structure of amyloid fibrils by synchrotron X-ray diffraction". J Mol Biol. 273 (3): 729–39. PMID 9356260. doi:10.1006/jmbi.1997.1348.
^ Rebecca, Nelson; M. Sawaya; M. Balbirnie; A. Madsen; C. Riekel; R. Grothe; D. Eisenberg (9 Jun 2005). "Structure of the cross-beta spine of amyloid-like fibrils". Nature. 435 (7043): 773–78. PMC 1479801 . PMID 15944695. doi:10.1038/nature03680.
^ Sawaya, Michael; Sambashivan S; Nelson R; Ivanova MI; Sievers SA; Apostol MI; Thompson MJ; Balbirnie M; Wiltzius JJ; McFarlane HT; Madsen AØ; Riekel C; Eisenberg D. (24 May 2007). "Atomic structures of amyloid cross-beta spines reveal varied steric zippers". Nature. 447 (7143): 453–57. PMID 17468747. doi:10.1038/nature05695.
^ Gilead S, Gazit E (August 2004). "Inhibition of amyloid fibril formation by peptide analogues modified with alpha-aminoisobutyric acid". Angew. Chem. Int. Ed. Engl. 43 (31): 4041–44. PMID 15300690. doi:10.1002/anie.200353565.
^ finder, v; glockshuber (2009). "The Recombinant Amyloid-β Peptide Aβ1–42 Aggregates Faster and Is More Neurotoxic than Synthetic Aβ1–42". Journal of Molecular Biology. 396 (1): 9–18. PMID 20026079. doi:10.1016/j.jmb.2009.12.016.
^ "State of Aggregation". Nature Neuroscience. 14 (4): 399. 2011. PMID 21445061. doi:10.1038/nn0411-399.
^ "BioPure Amyloid Peptides".
^ Morley, JF; Brignull, HR; Weyers, JJ; Morimoto, RI (Aug 2002). "The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans". Proc Natl Acad Sci U S A. 99 (16): 10417–22. PMC 124929 . PMID 12122205. doi:10.1073/pnas.152161099.
^ Gazit E (January 2002). "A possible role for pi-stacking in the self-assembly of amyloid fibrils". FASEB J. 16 (1): 77–83. PMID 11772939. doi:10.1096/fj.01-0442hyp.
^ Pawar A. P.; Dubay K. F.; et al. (2005). "Prediction of "Aggregation-prone" and "Aggregation-susceptible" Regions in Proteins Associated with Neurodegenerative Diseases". J Mol Biol. 350 (2): 379–92. PMID 15925383. doi:10.1016/j.jmb.2005.04.016.
^ Jackson, K.; Barisone, G. A.; Diaz, E.; Jin, L.-w.; DeCarli, C. & Despa, F. (2013). "Amylin deposition in the brain: A second amyloid in Alzheimer disease?". Annals of Neurology. 74 (4): 517–526. PMC 3818462 . PMID 23794448. doi:10.1002/ana.23956.
^ Wise-Scira O, Xu L, Kitahara T, Perry G, Coskuner O (October 2011). "Amyloid-β peptide structure in aqueous solution varies with fragment size". Journal of Chemical Physics. 135 (1): 205101–11. PMID 22128957. doi:10.1063/1.3662490.
^ Kachooei E, Moosavi-Movahedi AA, Khodagholi F, Ramshini H, Shaerzadeh F, Sheibani N (July 2012). "Oligomeric Forms of Insulin Amyloid Aggregation Disrupt Outgrowth and Complexity of Neuron-Like PC12 Cells". PLOS ONE. 7 (7): e41344. PMC 3407202 . PMID 22848469. doi:10.1371/journal.pone.0041344.
^ Demuro A, Mina E, Kayed R, Milton SC, Parker I, Glabe CG (April 2005). "Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers". The Journal of Biological Chemistry. 280 (17): 17294–300. PMID 15722360. doi:10.1074/jbc.M500997200.
^ Kagan BL, Azimov R, Azimova R (2004-11-01). "Amyloid Peptide Channels". J Membrane Biol. 202 (1): 1–10. doi:10.1007/s00232-004-0709-4.
^ Kadowaki, H; et al. (2005). "Amyloid beta induces neuronal cell death through ROS-mediated ASK1 activation". Cell Death Differ. 12 (1): 19–24. PMID 15592360. doi:10.1038/sj.cdd.4401528.
^ Kochneva-Pervukhova, NV; Alexandrov, AI; Ter-Avanesyan, MD (2012). Tuite, Mick F, ed. "Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast". PLOS ONE. 7 (1): e29832. PMC 3256205 . PMID 22253794. doi:10.1371/journal.pone.0029832.
^ Nesterov, Evgueni E.; et al. (2005). "In Vivo Optical Imaging of Amyloid Aggregates in Brain: Design of Fluorescent Markers". Angewandte Chemie International Edition. 44 (34): 5452–56. PMID 16059955. doi:10.1002/anie.200500845.
^ Bae, Sohyeon; et al. (2015). "Torsion-dependent fluorescence switching of amyloid-binding dye NIAD-4". Chemical Physics Letters. 633: 109–13. doi:10.1016/j.cplett.2015.05.010.

External links

Dutch forum
[1] Amyloidosis Foundation
Bacterial Inclusion Bodies Contain Amyloid-Like Structure at SciVee
Amyloid Cascade Hypothesis
Stanford University Amyloid Center
Amyloid Treatment and Research Program at Boston University
Amyloid: Journal of Protein Folding Disorders web page at InformaWorld
Information, support and advice to anyone with Amyloidosis, particularly in Australia (www.amyloidosisaustralia.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
National Kidney and Urologic Diseases Information Clearinghouse at National Institute of Health
Role of anesthetics in Alzheimer's disease: Molecular details revealed
Mini Review Amyloidosis Covering structure, mechanisms of action and kinetics of amyloid fibrils.
Video of amyloid formation.

UpToDate Contents

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1. アミロイドーシスの概要 an overview of amyloidosis
2. アミロイド疾患の遺伝的要因 genetic factors in the amyloid diseases
3. アミロイドーシスの筋骨格系の症状 musculoskeletal manifestations of amyloidosis
4. 消化管アミロイドーシス gastrointestinal amyloidosis
5. アミロイド心筋症 amyloid cardiomyopathy

English Journal

Potential Use of Lactosylated Dendrimer (G3)/α-Cyclodextrin Conjugates as Hepatocyte-Specific siRNA Carriers for the Treatment of Familial Amyloidotic Polyneuropathy.

Hayashi Y, Mori Y, Yamashita S, Motoyama K, Higashi T, Jono H, Ando Y, Arima H.SourceDepartment of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Molecular pharmaceutics.Mol Pharm.2012 Jun 4;9(6):1645-53. Epub 2012 Apr 30.
To reveal the potential use of lactosylated-dendrimer (G3) conjugates with α-cyclodextrin (Lac-α-CDE (G3)) as novel hepatocyte-specific siRNA carriers in order to treat transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP), we evaluated the RNAi effect of siRNA complexes with Lac-�
PMID 22510029

VIIIth International Symposium of Familial Amyloidotic Polyneuropathy and VIIth International Workshop on Liver Transplantation in Familial Amyloidotic Polyneuropathy: Organizing Committee.

[No authors listed]
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.Amyloid.2012 Jun;19 Suppl 1:i-iii.
PMID 22620972

Japanese Journal

遺伝性神経難病の発症前遺伝子診断を受けて生きる人の体験 : 家族性アミロイドポリニューロパチー家系員の語りの分析

柊中智恵子,中込さと子,川崎裕美 [他]
日本看護科学会誌 33(2), 40-50, 2013-06
NAID 40019765424

家族性トランスサイレチン眼アミロイドーシスへの網膜光凝固術

川路隆博
日本眼科學会雜誌 116(11), 1046-1051, 2012-11-10
NAID 10031129938

本邦で最初のトランスサイレチンThr49Ala変異による家族性アミロイドポリニューロパチーの1例

宇田憲司,酒井竜一郎,出井里佳 [他],岩井克成,杢野謙次
日本内科学会雑誌 100(10), 3028-3030, 2011-10-10
症例は54歳，女性．両側足底のしびれ感で発症．4年後の入院時には，四肢遠位部優位の感覚運動障害，自律神経障害など認めた．末梢神経生検にてアミロイドの沈着を認め，家族性アミロイドポリニューロパチー（FAP）と診断した．遺伝子検査により，本邦では最初のトランスサイレチン，Thr49Ala変異であることが判明した．臨床像は既報告のフランス，イタリアの例に類似していた．
NAID 10030390336

Related Pictures

★リンクテーブル★

リンク元	「家族性アミロイドーシス」「家族性アミロイド神経障害」
関連記事	「familial」

「家族性アミロイドーシス」

　　[★]

英: familial amyloidosis
同: 遺伝性アミロイドーシス hereditary amyloidosis、AF amyloidosis
関: アミロイドーシス

概念

variant plasma proteinがアミロイドとして沈着することにより発症するアミロイドーシスの一型。

分類

アミロイドーシスの病型	アミロイド蛋白	前駆体蛋白
FAP I	ATTR	トランスサイレチン
FAP II	ATTR	トランスサイレチン
FAP III	AApoA1	アポA1
FAP IV	AGel1	ゲルソリン
家族性地中海熱	AA	アポSAA
Muckle-Wells症候群	AA	アポSAA

遺伝形式

常染色体優性遺伝

疫学

HIM.2148

まれ、罹患率<1/10万人
中年発症
(Ile122変異の型は)アフリカ系アメリカ人に多く、変異の頻度は4%である。

症候