Reactome: A Curated Pathway Database

Amyloid precursor proteins form ordered fibrils (R-HSA-977136)

Species Homo sapiens

Summation

Amyloid fibril formation is associated with a wide range of diseases (Chiti & Dobson 2006), though the accumulation and deposition of fibrillar material does not correlate well with disease pathogenesis and it is now widely believed that oligomeric amyloid forms are largely responsible for the cytotoxic effects of amyloid (Glabe 2009). Fibrils have been described as more like crystalline polymer structures than the protein monomers they are derived from (Wetzel et al. 2007). Fibril formation is usually preceded by the association of monomers into oligomeric structures (Kodali & Wetzel 2007). For Beta-amyloid, these are spherical structures with around 12 units (Bernstein et al. 2005). Larger structures called protofibrils are also observed, non-spherical filamentous structures lacking a periodic substructure (Goldsbury 2005).

Locations in the PathwayBrowser
Additional Information
Compartment extracellular region
Diseases
Name Identifier Synonyms
Amyloidosis 9120
Literature References
pubMedId Title Journal Year
8159701 Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition Proc Natl Acad Sci U S A 1994
9862427 Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson's disease FEBS Lett 1998
2118650 Immunoglobulin heavy-chain-associated amyloidosis Proc Natl Acad Sci U S A 1990
3080684 Serum levels of beta 2-microglobulin as a new form of amyloid protein in patients undergoing long-term hemodialysis N Engl J Med 1986
279930 Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy Proc Natl Acad Sci U S A 1978
1270801 Isolation and partial characterization of SAA-an amyloid-related protein from human serum J Immunol 1976
3142462 Variant apolipoprotein AI as a major constituent of a human hereditary amyloid Biochem Biophys Res Commun 1988
11401442 A new human hereditary amyloidosis: the result of a stop-codon mutation in the apolipoprotein AII gene Genomics 2001
11467836 Codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR) amyloidosis Biochem Biophys Res Commun 2001
1849145 Gelsolin-related amyloidosis. Identification of the amyloid protein in Finnish hereditary amyloidosis as a fragment of variant gelsolin J Clin Invest 1991
8464497 Human lysozyme gene mutations cause hereditary systemic amyloidosis Nature 1993
8097946 Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain Nat Genet 1993
2900981 Mutation in cystatin C gene causes hereditary brain haemorrhage Lancet 1988
10391242 A stop-codon mutation in the BRI gene associated with familial British dementia Nature 1999
18449172 Leukocyte chemotactic factor 2: A novel renal amyloid protein Kidney Int 2008
8490014 The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease Biochemistry 1993
3094007 Assignment of the human and mouse prion protein genes to homologous chromosomes Proc Natl Acad Sci U S A 1986
3035556 Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells Proc Natl Acad Sci U S A 1987
2195544 Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation Proc Natl Acad Sci U S A 1990
1837051 Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide-like immunoreactivity J Pathol 1991
9006323 Prolactin-derived amyloid in the aging pituitary gland Am J Pathol 1997
3053705 An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing J Biol Chem 1988
10411933 Medin: an integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid Proc Natl Acad Sci U S A 1999
9054935 Kerato-epithelin mutations in four 5q31-linked corneal dystrophies Nat Genet 1997
8870004 Localized amyloidosis of the seminal vesicle: identification of lactoferrin immunoreactivity in the amyloid material Pathol Int 1996
18484335 Odontogenic ameloblast-associated protein nature of the amyloid found in calcifying epithelial odontogenic tumors and unerupted tooth follicles Amyloid 2008
15962837 Senile seminal vesicle amyloid is derived from semenogelin I J Lab Clin Med 2005