Editing Amyloid (section)

{{short description|Insoluble protein aggregate with a fibrillar morphology}}
{{Other uses}}
<!--[[File:Crossbeta.png|300px|thumb|right|Structural model of a section of cross-β amyloid fibril. The closest monomer units are highlighted. Note that each monomer contributes a β strand to a β sheet that extends the full length of the fibril. In this example, the fibril comprises four β sheets, with each monomer contributing two strands to two different sheets. Hydrogen bonding occurs in an intermolecular fashion. The strands are oriented perpendicular to long axis of the fibril.]]-->
[[File:Small bowel duodenum with amyloid deposition 20X.jpg|thumb|[[Micrograph]] showing amyloid deposits (pink) in [[small bowel]]. Duodenum with amyloid deposition in lamina propria. Amyloid shows up as homogeneous pink material in lamina propria and around blood vessels. 20× magnification. ]]
'''Amyloids''' are aggregates of [[protein]]s characterised by a [[fibril]]lar morphology of typically 7–13 [[Nanometer|nm]] in [[diameter]], a [[beta sheet|β-sheet]] [[Secondary structure of proteins|secondary structure]] (known as cross-β) and ability to be [[Staining|stained]] by particular dyes, such as [[Congo red]].<ref name="pmid9356260">{{cite journal | vauthors = Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CC | s2cid = 19394482 | title = Common core structure of amyloid fibrils by synchrotron X-ray diffraction | journal = Journal of Molecular Biology | volume = 273 | issue = 3 | pages = 729–39 | date = October 1997 | pmid = 9356260 | doi = 10.1006/jmbi.1997.1348 }}</ref> In the [[human body]], amyloids have been linked to the development of various [[disease]]s.<ref name="pmid28498720"/> Pathogenic amyloids form when previously healthy proteins lose their normal [[Protein structure|structure]] and [[physiology|physiological]] functions ([[Protein misfolding|misfolding]]) and form fibrous deposits within and around cells. These protein misfolding and deposition processes disrupt the healthy function of tissues and organs.

Such amyloids have been associated with (but not necessarily as the cause of) more than 50<ref name="pmid28498720">{{cite journal | vauthors = Chiti F, Dobson CM | title = Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade | journal = Annual Review of Biochemistry | volume = 86 | pages = 27–68 | date = June 2017 | pmid = 28498720 | doi = 10.1146/annurev-biochem-061516-045115 | hdl = 2158/1117236 | hdl-access = free }}</ref><ref name="pmid30614283">{{cite journal | vauthors = Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva MJ, Sekijima Y, Sipe JD, Westermark P | display-authors = 6 | title = Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee | journal = Amyloid | volume = 25 | issue = 4 | pages = 215–219 | date = December 2018 | pmid = 30614283 | doi = 10.1080/13506129.2018.1549825 | doi-access = free | hdl = 1805/20251 | hdl-access = free }}</ref> human diseases, known as [[amyloidosis]], and may play a role in some [[neurodegenerative diseases]].<ref name="pmid28498720"/><ref>{{cite journal | vauthors = Pulawski W, Ghoshdastider U, Andrisano V, Filipek S | title = Ubiquitous amyloids | journal = Applied Biochemistry and Biotechnology | volume = 166 | issue = 7 | pages = 1626–43 | date = April 2012 | pmid = 22350870 | pmc = 3324686 | doi = 10.1007/s12010-012-9549-3 }}</ref> Some of these diseases are mainly sporadic and only a few cases are [[Genetic disorder|familial]]. Others are only [[Genetic disorder|familial]]. Some [[iatrogenic|result from medical treatment]]. [[Prion]]s are an [[infectious]] form of amyloids that can act as a template to convert other non-infectious forms.<ref>{{cite journal | vauthors = Soto C, Estrada L, Castilla J | title = Amyloids, prions and the inherent infectious nature of misfolded protein aggregates | journal = Trends in Biochemical Sciences | volume = 31 | issue = 3 | pages = 150–5 | date = March 2006 | pmid = 16473510 | doi = 10.1016/j.tibs.2006.01.002 }}</ref> Amyloids may also have normal biological functions; for example, in the formation of [[fimbria (bacteriology)|fimbriae]] in some [[genus|genera]] of [[bacteria]], transmission of epigenetic traits in fungi, as well as pigment deposition and hormone release in humans.<ref name="ann rev biochem 2011"/>

Amyloids have been known to arise from many different proteins.<ref name="pmid28498720"/><ref>{{cite journal | vauthors = Ramirez-Alvarado M, Merkel JS, Regan L | title = A systematic exploration of the influence of the protein stability on amyloid fibril formation in vitro | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 16 | pages = 8979–84 | date = August 2000 | pmid = 10908649 | pmc = 16807 | doi = 10.1073/pnas.150091797 | bibcode = 2000PNAS...97.8979R | doi-access = free }}</ref> These polypeptide chains generally form [[beta sheet|β-sheet]] structures that aggregate into long fibers; however, identical polypeptides can fold into multiple distinct amyloid conformations.<ref name="pm11076514"/> The diversity of the conformations may have led to different forms of the [[prion]] diseases.<ref name="ann rev biochem 2011">{{cite journal | vauthors = Toyama BH, Weissman JS | title = Amyloid structure: conformational diversity and consequences | journal = Annual Review of Biochemistry | volume = 80 | pages = 557–85 | date = 2011 | pmid = 21456964 | pmc = 3817101 | doi = 10.1146/annurev-biochem-090908-120656 }}</ref>

An unusual secondary structure named [[alpha sheet|α sheet]] has been proposed as the toxic constituent of amyloid precursor proteins,<ref name="alphasheet">{{cite journal | vauthors = Armen RS, Demarco ML, Alonso DO, Daggett V | title = Pauling and Coreys α-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 1 | pages = 11622–11627 | date = 2004 | pmid = 15280548 | pmc = 511030 | doi = 10.1073/pnas.0401781101  | bibcode = 2004PNAS..10111622A | doi-access = free }}</ref> but this idea is not widely accepted at present.

[[File:2rnm.jpg|thumb|upright=1.1|Amyloid of HET-s(218-289) prion pentamer, ''Podospora anserina'' ({{PDB|2rnm}})]]