Name Aggregation Function Pathologies Listed sequences
(Apo)-Serum amyloid A Amyloid Serum amyloid A is an acute phase protein. It is expressed mainly in the liver. Though its role is not well understood, it is involved in cholesterol regulation, activation of secretory cholesterol phospholipases, and mediation of monocytes, granulocytes and T-cells. It also possess inhibitory effects on inflammation. SAA is a precursor protein in inflammation-associated reactive amyloidosis (AA-type). Among the 3 human isoforms, only SAA1 and SAA2 have been identified in amyloid aggregates. 74
(Pro)-Calcitonin Amyloid Calcitonin is a 32 residues peptide hormone, produced by the thyroid gland in humans. It lowers plasma calcium and phosphate levels without augmenting calcium accretion. In medullary thyroid cancer (MTC), calcitonin produced by tumorous cells forms amyloid deposits. 37
A-beta protein precursor Amyloid The APP (Amyloid Precursor Protein) comprises a large extracellular N-terminal domain, a short hydrophobic membrane-spanning domain, and a short C-terminal region. The 40-residue Abeta is a proteolytic product of this protein, encompassing the end of the N-terminal region and the transmembrane domain. Aberrant catabolism of APP seems to lead to the formation of Abeta. This peptide is implicated in the pathogenesis of Alzheimer's disease and aged Down's Syndrome (which is promoted by the acquisition of an additional copy of chromosome 21).
In Alzheimer's disease, the brain is characterised by extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and vascular and neuronal damage. The major peptide found within these deposits is Abeta.
125
A-S2C casein Amyloid 0
ABriPP/ADanPP Amyloid This highly insoluble peptide is a fragment of a putative type-II single-spanning transmembrane precursor. The Familial British Dementia (FBD), also called familial cerebral amyloid angiopathy-British type, is due to a single base substitution at the stop codon of the BRI gene. This mutation generates a 27 aa protein, wich 34 carboxy-terminal amino acids form the ABri peptide found in amyloid aggregates of FBD. 3
Alpha Synuclein Amyloid It is a presynaptic protein, the function of wich is still not fully understood. It might be involved in the modulation of synaptic transmission, in the regulation of the localization of vesicles in synapses, and in neuronal plasticity. Alpha synuclein is involved in several neurodegenerative pathologies, called synucleinopathies, such as Alzheimer's and Parkinson's diseases, or progressive autonomic failure and neurodegeneration with type 1 brain iron accumulation.
A 35 residues fragment, called NAC, has been found in senile plaques and Lewy bodies typical of Alzheimer's and Parkinson's diseases, while two mutations (Ala35Pro and Ala 53Thr) lead to the accumulation of the entire protein in Lewy bodies.
21
Apolipoprotein A I Amyloid It plays a critical role in lipid metabolism : it is the major protein component of high density lipoprotein particles and plays a key role in the solubilization of lipids in these particles, the activation of lecithin cholesterol acyltransferase, the binding of high density lipoprotein to cell surfaces, and the promotion of cholesterol efflux from cells. The N-terminal region of apolipoprotein A-1 has been found in amyloid fibrils of autosomal dominant systemic amyloidosis. Those amyloidosis are due to either the wild type apolipoprotein A1, or mutants of this protein, like Arg84 or Iowa variants. 54
Apolipoprotein A II Amyloid It plays a critical role in lipid metabolism : it is the major protein component of high density lipoprotein particles and plays a key role in the solubilization of lipids in these particles, the activation of lecithin cholesterol acyltransferase, the binding of high density lipoprotein to cell surfaces, and the promotion of cholesterol efflux from cells. 0
Apolipoprotein A IV Amyloid It plays a critical role in lipid metabolism : it is the major protein component of high density lipoprotein particles and plays a key role in the solubilization of lipids in these particles, the activation of lecithin cholesterol acyltransferase, the binding of high density lipoprotein to cell surfaces, and the promotion of cholesterol efflux from cells. 0
Atrial natriuretic factor Amyloid The atrial natriuretic factor plays an important role in the homeostasis of blood pressure as well as in sodium balance. Aggregates containing the atrial natiurectic factor are characteristic of the Isolated Atrial Amyloid (IAA), a very common age-related amyloid form only seen in the atria of the heart. 34
Beta 2 Microglobulin Amyloid Beta 2 Microglobulin is the non-covalently bound light-chain of the class I human leukocyte antigen (HLA class 1). Beeing normally degraded by kidneys, serum beta 2 microglobulin accumulates in case of renal failure, leading to the aggregation of the full length protein, mosttly in the musculoskeletal system. 141
Corneodesmin Amyloid 0
Cystatin C Amyloid Cystatin C, as well as other cystatins, is a natural cysteine protease inhibitor. Wild type cystatin C has been shown to accumulate within amyloid-beta (A beta) amyloid deposits in Alzheimer's disease (AD) brain. Aggregation of calcitonin is also involved in sporadic cerebral amyloid angiopathy, while a variant human cystatin C (L68Q) is responsible for autosomal dominant cerebral amyloid angiopathy. 67
Fibrinogen alpha Amyloid Fibrinogen is an acute phase protein as well as a component of the coagulation cascade. It is found in hexameres of alpha, beta and gamma chains. Arg554Leu and Glu526Val mutations are responsible for autosomal dominant hereditary hepatic or renal amyloidosis. 59
Galectin Amyloid 0
Gelsolin Amyloid This calcium-dependent actin-binding protein modulates actin filament length. It thus influences the structure of the cytoskeleton and plays a key role in cellular motility and differentiation. Wild-type gelsolin is normally stabilized by Ca2+ binding. This stabilization lacks in D187N and D187Y variants, allowing access to a furin cleavage site. Furin processing liberates an amyloidogenic fragment, which aggregation leads to gelsolin familial amyloidosis. 39
Huntingtin Amyloid Huntingtin is involved in fast axonal trafficking. Polyglutamine expansion in the N-terminal region of huntingtin plays a central role in Huntington's disease, by causing protein aggregation that leads to neurotoxicity. 19
Immunoglobulin heavy chain Amyloid Immunoglobulins are large glycoproteins that are secreted by plasma cells. They are acting as antibodies in the immune response by binding with specific antigens. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM. 0
Immunoglobulin light chain Amyloid Immunoglobulins are large glycoproteins that are secreted by plasma cells. They are acting as antibodies in the immune response by binding with specific antigens. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM. Light-chain (L-chain) amyloidosis is characterized by deposition of fibrillar aggregates composed of the N-terminal L-chain variable region (VL) domain of an immunoglobulin, generally in individuals overproducing a monoclonal L chain. 0
Insulin Amyloid This hormone is secreted by the islets of Langerhans, and is involved in the regulation of the metabolism of carbohydrates and fats, especially the conversion of glucose to glycogen, which lowers the blood glucose level. Localised amyloidosis has been shown at the sites of injections for a patient with type 1 (insulin-dependent) diabete. Insulin aggregates have also been found in insulin infusion pump. 160
Islet amyloid polypeptide Amyloid IAPP is an hormone produced by pancreatic beta cells, that moderates the glucose lowering effects of insulin. IAPP is the peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients and in insulinomas. 17
Kerato-epithelin Amyloid 0
Lactadherin Amyloid This glycoprotein was previously known to be expressed by mammary epithelial cells as a cell surface protein and secreted as part of the milk fat globule membrane. But recently, it was found to be expressed by aortic medial smooth muscle cells. A possible function has been shown in vitro : lactadherin might act as an anticoagulant, by competing with blood coagulation proteins for phospholipid binding sites. The aggregation of a 50 residues fragment of lactadherin, called medin, leads to aortic medial amyloid, a form of localized amyloid very common in individuals older than 60 years. But the importance and effects of those amyloid deposits remain unknown. 5
Lactoferrin Amyloid Lactoferrin is a red iron-binding protein synthesized by neutrophils and glandular epithelial cells. It is found in many human secretions (as tears and milk), retarding bacterial and fungal growth. Amyloid deposits containing lactoferrin have been discovered in the cornea, seminal vesicles, and brain. 34
Leukocyte chemotactic factor-2 Amyloid 0
Lung surfactant protein Amyloid This 35-residues protein is the major component of lung surfactant. The conformation of SP-C can change from a monomeric alpha-helix to beta-sheet aggregates involved in the pulmonary alveolar proteinosis (PAP). 16
Lysozyme Amyloid It is an enzyme occurring naturally in egg white, human tears, saliva, and other body fluids, capable of degrading peptidoglycane and thereby acting as a mild antiseptic. Mutations in the lysozyme gene can lead to the aggregation of the human protein, therefore to non-neuropathic systemic amyloidosis. 122
Odontogenic ameloblast-associated protein Amyloid 0
Prion Protein Amyloid Although the actual function of PrP remains unknown, many hypothesis are proposed, such as involvement in signal transmission or in copper regulation, as well as a possible function of copper-dependent superoxide dismutase. PrP is the well-known prion protein of mammals. Its prionic form leads to many neurodegenerative diseases, including transmissible spongiform encephalopathies (scrapie in sheep, bovine spongiform encephalopathy in cattle or Creutzfeldt-Jacob disease and Gerstmann-Straussler-Scheinker syndrome in humans) and some dementias. 353
Prolactin Amyloid Prolactin is involved in a wide variety of biological processes, among wich are osmoregulation, development, reproduction, or immune regulation. This hormone constitutes the amyloid fibrils of pituitary glands of aging individuals. 112
Semenogelin 1 Amyloid 0
Tau Amyloid Tau binds to and regulates the assembly and stability of neuronal microtubules. Tau proteins are found in extracellular aggregates associated with Alzheimer's disease. Those proteins are also involved in many dementia, usually due to defects in the Tau gene. 37
Transthyretin Amyloid Transthyretin is a plasma protein that transports thyroxine. It can also form complexes with retinol binding proteins, so that those proteins are not lost by filtration in the kidney. Single site mutations are associated with familial amyloid polyneuropathy (FAP). Those mutations destabilize tetrameric TTR, inducing monomeric amyloidogenic intermediates apparition. Those intermediates assembles into amyloid fibrils, whereas wild-type TTR remains tetrameric and nonamyloidogenic. 54