Amyloid

For other uses, see Amyloid (disambiguation).
Micrograph showing amyloid deposits (pink) in small bowel. H&E stain.

Amyloids are aggregates of proteins that become folded into the wrong shape, allowing many copies of that protein to stick together. These previously healthy proteins most often lose their normal function and form large fibrils. These fibrils disrupt the healthy physiological function of nearby tissues and organs.

Amyloids have been known to arise from at least 18 different proteins and polypeptides,[1] and have been associated with more than 20 human diseases, known as amyloidosis, and may play a role in some neurodegenerative disorders.[2]

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.[3]

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

The remainder of this article will use the biophysical context.

Diseases featuring amyloids

Disease Protein featured Official abbreviation
Alzheimer's disease Beta amyloid[8][9][10] Aβ
Diabetes mellitus type 2 IAPP (Amylin)[11][12] AIAPP
Parkinson's disease Alpha-synuclein[9] none
Transmissible spongiform encephalopathy (e.g. bovine spongiform encephalopathy) PrPSc[13] APrP
Fatal familial insomnia PrPSc APrP
Huntington's disease Huntingtin[14][15] none
Medullary carcinoma of the thyroid Calcitonin[16] 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[17] Aβ
Cerebral amyloid angiopathy (Icelandic type) Cystatin ACys
Systemic AL amyloidosis Immunoglobulin light chain AL[16] AL
Sporadic Inclusion body myositis S-IBM none

The International Society of Amyloidosis classifies amyloid fibrils based upon associated proteins.[18]

Non-disease and functional amyloids

"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

Amyloid is characterized by a cross-beta sheet quaternary structure. 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.[30] 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.[31] 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.

Recent X-ray diffraction studies of microcrystals revealed atomistic details of core region of amyloid.[32][33] In the crystallographic structure, short stretches from amyloid-prone regions of amyloidogenic proteins run perpendicular to the filament axis, confirming the "cross-beta" model. In addition, two layers of beta-sheet interdigitate to create compact dehydrated interface termed as steric-zipper interface. 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.

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.[34] 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. 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.[35] 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.[36] Consequently, there has been renewed efforts to manufacture Amyloid beta 1-42 and other amyloid peptides at unprecedented (>99%) purity.[37]

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. 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.[38]

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.[39][40]

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. 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.[41] 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. Polypeptides will not cross-polymerize their mirror-image counterparts, indicating that the phenomenon involves specific binding and recognition events.

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.[42]

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.[43]

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.[10][44]

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.[45]

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.[46]

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.[47]

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.[48] In general, this is attributed to the environmental change, as these dyes intercalate between beta-strands to confine their structure.[49] 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.

See also

References

  1. ↑ Marina Rami´rez-Alvarado, Jane S. Merkel, and Lynne Regan (2000). "A systematic exploration of the influence of the protein stability on amyloid fibril formation in vitro". PNAS 97 (16): 8979–8984. doi:10.1073/pnas.150091797. PMC 16807. PMID 10908649.
  2. ↑ Pulawski, W; Ghoshdastider, U; Andrisano, V; Filipek, S (2012). "Ubiquitous amyloids". Applied Biochemistry and Biotechnology 166 (7): 1626–43. doi:10.1007/s12010-012-9549-3. PMC 3324686. PMID 22350870.
  3. ↑ Kyle R.A. (2001). "Amyloidosis: a convoluted story". Brit. J. Haem. 114 (3): 529–538. doi:10.1046/j.1365-2141.2001.02999.x. PMID 11552976.
  4. ↑ Sipe J. D., Cohen A.S.; Cohen (2000). "Review: History of the Amyloid Fibril". J. Struct. Biol. 130 (2–3): 88–98. doi:10.1006/jsbi.2000.4221. PMID 10940217.
  5. ↑ 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. doi:10.2337/db06-1579. PMID 17353506.
  6. ↑ Nilsson MR (September 2004). "Techniques to study amyloid fibril formation in vitro". Methods (San Diego, Calif.) 34 (1): 151–60. doi:10.1016/j.ymeth.2004.03.012. PMID 15283924.
  7. ↑ 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. doi:10.1007/s00018-007-7110-2. PMID 17530168.
  8. ↑ Chiang PK, Lam MA, Luo Y; Lam; Luo (September 2008). "The many faces of amyloid beta in Alzheimer's disease". Current molecular medicine 8 (6): 580–4. doi:10.2174/156652408785747951. PMID 18781964.
  9. 1 2 Irvine GB, El-Agnaf OM, Shankar GM, Walsh DM; El-Agnaf; Shankar; Walsh (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. doi:10.2119/2007-00100.Irvine. PMC 2274891. PMID 18368143.
  10. 1 2 Ferreira ST, Vieira MN, De Felice FG; Vieira; De Felice (2007). "Soluble protein oligomers as emerging toxins in Alzheimer's and other amyloid diseases". IUBMB Life 59 (4–5): 332–45. doi:10.1080/15216540701283882. PMID 17505973.
  11. ↑ Haataja L, Gurlo T, Huang CJ, Butler PC; Gurlo; Huang; Butler (May 2008). "Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis". Endocrine Reviews 29 (3): 303–16. doi:10.1210/er.2007-0037. PMC 2528855. PMID 18314421.
  12. ↑ Höppener JW, Ahrén B, Lips CJ; Ahrén; Lips (August 2000). "Islet amyloid and type 2 diabetes mellitus". The New England Journal of Medicine 343 (6): 411–9. doi:10.1056/NEJM200008103430607. PMID 10933741.
  13. ↑ "More than just mad cow disease". Nature Structural Biology 8 (4): 281. 2001. doi:10.1038/86132.
  14. ↑ Truant R, Atwal RS, Desmond C, Munsie L, Tran T; Atwal; Desmond; Munsie; Tran (September 2008). "Huntington's disease: revisiting the aggregation hypothesis in polyglutamine neurodegenerative diseases". The FEBS Journal 275 (17): 4252–62. doi:10.1111/j.1742-4658.2008.06561.x. PMID 18637947.
  15. ↑ Weydt P, La Spada AR; La Spada (August 2006). "Targeting protein aggregation in neurodegeneration--lessons from polyglutamine disorders". Expert opinion on therapeutic targets 10 (4): 505–13. doi:10.1517/14728222.10.4.505. PMID 16848688.
  16. 1 2 "Amyloidosis, Overview" by Bruce A Baethge and Daniel R Jacobson
  17. ↑ Dotti CG, De Strooper B; De Strooper (February 2009). "Alzheimer's dementia by circulation disorders: when trees hide the forest". Nat. Cell Biol. 11 (2): 114–6. doi:10.1038/ncb0209-114. PMID 19188916.
  18. ↑ 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): 101–104. doi:10.3109/13506129.2010.526812. PMID 21039326.
  19. ↑ Hammer ND, Wang X, McGuffie BA, Chapman MR; Wang; McGuffie; Chapman (May 2008). "Amyloids: friend or foe?". Journal of Alzheimer's disease : JAD 13 (4): 407–19. PMC 2674399. PMID 18487849.
  20. ↑ Dueholm M. S., Albertsen M., Otzen D., Nielsen P. H.; Albertsen; Otzen; Nielsen (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. doi:10.1371/journal.pone.0051274. PMC 3521004. PMID 23251478.
  21. ↑ 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): 3479–3484. doi:10.1074/jbc.M111.313049. PMID 22147705.
  22. ↑ 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.; Petersen; Sønderkær; Larsen; Christiansen; Hein; Enghild; Nielsen; Nielsen; Nielsen; Otzen (2010). "Functional amyloid in Pseudomonas". Mol Microbiol 77 (4): 1009–1020. doi:10.1111/j.1365-2958.2010.07269.x. PMID 20572935.
  23. ↑ 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.; Søndergaard; Nilsson; Christiansen; Stensballe; Overgaard; Givskov; Tolker-Nielsen; Otzen; Nielsen (2013). "Expression of Fap amyloids in Pseudomonas aeruginosa, P. fluorescens, and P. putida results in aggregation and increased biofilm formation". Microbiologyopen 2 (3): 365–382. doi:10.1002/mbo3.81. PMC 3684753. PMID 23504942.
  24. ↑ Maji, S.K.; et al. (2009). "Functional Amyloids As Natural Storage of Peptide Hormones in Pituitary Secretory Granules". Science 325 (5938): 328–332. doi:10.1126/science.1173155. PMID 19541956.
  25. ↑ Bongiovanni, M.N.; et al. (2011). "Functional fibrils derived from the peptide TTR1-cycloRGDfK that target cell adhesion and spreading". Biomaterials 26 (26): 6099–110. doi:10.1016/j.biomaterials.2011.05.021. PMID 21636126.
  26. ↑ Larsen P., Nielsen J. L., Dueholm M. S., Wetzel R., Otzen D., Nielsen P. H.; Nielsen; Dueholm; Wetzel; Otzen; Nielsen (2007). "Amyloid adhesins are abundant in natural biofilms". Environ Microbiol 9 (12): 3077–3090. doi:10.1111/j.1462-2920.2007.01418.x. PMID 17991035.
  27. ↑ 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. doi:10.1371/journal.pone.0017632. PMC 3050909. PMID 21408122.
  28. ↑ 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. doi:10.1016/j.tim.2011.10.002. PMC 3278544. PMID 22099004.
  29. ↑ Dueholm, M.S.; et al. (2015). "The Tubular Sheaths Encasing Methanosaeta thermophila Filaments are Functional Amyloids". J Biol Chem. doi:10.1074/jbc.M115.654780. PMID 26109065.
  30. ↑ Wormell RL. New fibres from proteins. Academic Press, 1954, pg 106.
  31. ↑ 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. doi:10.1006/jmbi.1997.1348. PMID 9356260.
  32. ↑ 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): 773–778. doi:10.1038/nature03680. PMC 1479801. PMID 15944695.
  33. ↑ 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): 453–457. doi:10.1038/nature05695. PMID 17468747.
  34. ↑ Gilead S, Gazit E; Gazit (August 2004). "Inhibition of amyloid fibril formation by peptide analogues modified with alpha-aminoisobutyric acid". Angew. Chem. Int. Ed. Engl. 43 (31): 4041–4. doi:10.1002/anie.200353565. PMID 15300690.
  35. ↑ 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. doi:10.1016/j.jmb.2009.12.016. PMID 20026079.
  36. ↑ Editor (2011). "State of Aggregation". Nature Neuroscience 14 (4): 399. doi:10.1038/nn0411-399. PMID 21445061.
  37. ↑ "BioPure Amyloid Peptides".
  38. ↑ 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. doi:10.1073/pnas.152161099.
  39. ↑ Gazit E (January 2002). "A possible role for pi-stacking in the self-assembly of amyloid fibrils". FASEB J. 16 (1): 77–83. doi:10.1096/fj.01-0442hyp. PMID 11772939.
  40. ↑ 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. doi:10.1016/j.jmb.2005.04.016. PMID 15925383.
  41. ↑ Jackson, K., Barisone, G. A., Diaz, E., Jin, L.-w., DeCarli, C. and Despa,F. (2013). "Amylin deposition in the brain: A second amyloid in Alzheimer disease?". Annals of Neurology 74 (4): n/a. doi:10.1002/ana.23956.
  42. ↑ Wise-Scira O, Xu L, Kitahara T, Coskuner O,; Xu; Kitahara; Perry; Coskuner (October 2011). "Amyloid-β peptide structure in aqueous solution varies with fragment size". Journal of Chemical Physics 135 (1): 205101–11. doi:10.1063/1.3662490.
  43. ↑ 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. doi:10.1371/journal.pone.0041344.
  44. ↑ Demuro A, Mina E, Kayed R, Milton SC, Parker I, Glabe CG; Mina; Kayed; Milton; Parker; Glabe (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. doi:10.1074/jbc.M500997200. PMID 15722360.
  45. ↑ 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.
  46. ↑ Kadowaki, H; et al. (2005). "Amyloid beta induces neuronal cell death through ROS-mediated ASK1 activation". Cell Death Differ 12 (1): 19–24. doi:10.1038/sj.cdd.4401528. PMID 15592360.
  47. ↑ 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. doi:10.1371/journal.pone.0029832. PMC 3256205. PMID 22253794.
  48. ↑ 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): 5452–5456. doi:10.1002/anie.200500845. PMID 16059955.
  49. ↑ Bae, Sohyeon; et al. (2015). "Torsion-dependent fluorescence switching of amyloid-binding dye NIAD-4". Chemical Physics Letters 633: 109–113. doi:10.1016/j.cplett.2015.05.010.

External links

Amyloid

Wikimedia Commons has media related to Amyloid.
This article is issued from Wikipedia - version of the Thursday, March 31, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.