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Amyloid fiber formation
Stable Identifier
R-HSA-977225
DOI
10.3180/r-hsa-977225.3
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Metabolism of proteins (Homo sapiens)
Amyloid fiber formation (Homo sapiens)
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Amyloid is a term used to describe deposits of fibrillar proteins, typically extracellular. The abnormal accumulation of amyloid, amyloidosis, is a term associated with tissue damage caused by amyloid deposition, seen in numerous diseases including neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's. Amyloid deposits consist predominantly of amyloid fibrils, rigid, non-branching structures that form ordered assemblies, characteristically with a cross beta-sheet structure where the sheets run parallel to the direction of the fibril (Sawaya et al. 2007). Often the fibril has a left-handed twist (Nelson & Eisenberg 2006). At least 27 human proteins form amyloid fibrils (Sipe et al. 2010). Many of these proteins have non-pathological functions; the trigger that leads to abnormal aggregations differs between proteins and is not well understood but in many cases the peptides are abnormal fragments or mutant forms arising from polymorphisms, suggesting that the initial event may be aggregation of misfolded or unfolded peptides. Early studies of Amyloid-beta assembly led to a widely accepted model that assembly was a nucleation-dependent polymerization reaction (Teplow 1998) but it is now understood to be more complex, with multiple 'off-pathway' events leading to a variety of oligomeric structures in addition to fibrils (Roychaudhuri et al. 2008), though it is unclear whether these intermediate steps are required in vivo. An increasing body of evidence suggests that these oligomeric forms are primarily responsible for the neurotoxic effects of Amyloid-beta (Roychaudhuri et al. 2008), alpha-synuclein (Winner et al. 2011) and tau (Dance & Strobel 2009, Meraz-Rios et al. 2010). Amyloid oligomers are believed to have a common structural motif that is independent of the protein involved and not present in fibrils (Kayed et al. 2003). Conformation dependent, aggregation specific antibodies suggest that there are 3 general classes of amyloid oligomer structures (Glabe 2009) including annular structures which may be responsible for the widely reported membrane permeabilization effect of amyloid oligomers. Toxicity of amyloid oligomers preceeds the appearance of plaques in mouse models (Ferretti et al. 2011).
Fibrils are often associated with other molecules, notably heparan sulfate proteoglycans and Serum Amyloid P-component, which are universally associated and seem to stabilize fibrils, possibly by protecting them from degradation.
Literature References
PubMed ID
Title
Journal
Year
16302959
Aspects on human amyloid forms and their fibril polypeptides
Westermark, P
FEBS J
2005
Participants
Events
SIAH1, SIAH2 bind SNCAIP
(Homo sapiens)
SIAH1, SIAH2 ubiquitinate SNCAIP
(Homo sapiens)
PARK2 binds SNCAIP
(Homo sapiens)
PARK2 K63-Ubiquitinates SNCAIP
(Homo sapiens)
SIAH1:UBE2L6:Ubiquitin binds SNCA
(Homo sapiens)
SIAH1:UBE2L6:Ubiquitin ubiquitinates SNCA
(Homo sapiens)
Ub-SNCA dissociates from the conjugating enzyme
(Homo sapiens)
USP9X binds Ub-SNCA
(Homo sapiens)
USP9X deubiquitinates Ub-SNCA
(Homo sapiens)
USP9X:SNCA dissociates
(Homo sapiens)
SNCAIP binds alpha-synuclein
(Homo sapiens)
Serum amyloid P-component forms homopentamers
(Homo sapiens)
NAT8,8B acetylate BACE1
(Homo sapiens)
BACE1 translocates from ER lumen to Golgi apparatus
(Homo sapiens)
FURIN cleaves 7K-BACE1 to 7K-BACE1(46-501)
(Homo sapiens)
Unknown deacetylase deacetylates 7K-BACE1(46-501)
(Homo sapiens)
BACE1(46-501) translocates from Golgi lumen to plasma membrane
(Homo sapiens)
BACE1 binds GGA1,2,3
(Homo sapiens)
BACE1:GGA1,2,3 translocates from plasma membrane to endosome
(Homo sapiens)
BACE1 cleaves APP(18-770) to APP(18-671) and APP(672-770)
(Homo sapiens)
Gamma-secretase cleaves APP(672-770) to APP(672-711) and APP(672-713)
(Homo sapiens)
APP(672-713),APP(672-711) translocate from endosome lumen to extracellular region
(Homo sapiens)
SORL1 binds APP(18-770)
(Homo sapiens)
SORL1 transports APP(18-770) from endosome lumen to Golgi lumen
(Homo sapiens)
Amyloid precursor proteins form ordered fibrils
(Homo sapiens)
Amyloid fibrils have additional components
(Homo sapiens)
Formation of serum amyloid P decamer
(Homo sapiens)
Serum amyloid P binds DNA and chromatin
(Homo sapiens)
CALB1 binds 4xCa2+
(Homo sapiens)
ADAM10:Zn2+ binds TSPANs
(Homo sapiens)
ADAM10:Zn2+:TSPANs translocates from ER lumen to plasma membrane
(Homo sapiens)
ADAM10:Zn2+:TSPANs cleaves APP(18-770)
(Homo sapiens)
APP translocates from plasma membrane to endosome lumen
(Homo sapiens)
Participates
as an event of
Metabolism of proteins (Homo sapiens)
Event Information
Go Biological Process
amyloid fibril formation (1990000)
Authored
Jupe, S (2010-10-15)
Reviewed
Perry, G (2011-04-08)
Perry, G (2015-11-09)
Created
Jupe, S (2010-10-15)
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