Protein folding pathology in domestic animals

Abstract

Fibrillar proteins form structural elements of cells and the extracellular matrix. Pathological lesions of fibrillar microanatomical structures, or secondary fibrillar changes in globular proteins are well known. A special group concerns histologically amorphous deposits, amyloid. The major characteristics of amyloid are: apple green birefringence after Congo red staining of histological sections, and non-branching 7−10 nm thick fibrils on electron microscopy revealing a high content of cross beta pleated sheets. About 25 different types of amyloid have been characterised. In animals, AA-amyloid is the most frequent type. Other types of amyloid in animals represent: AIAPP (in cats), AApoAI, AApoAII, localised AL-amyloid, amyloid in odontogenic or mammary tumors and amyloid in the brain. In old dogs Aβ and in sheep APrP sc -amyloid can be encountered. AA-amyloidosis is a systemic disorder with a precursor in blood, acute phase serum amyloid A (SAA). In chronic inflammatory processes AA-amyloid can be deposited. A rapid crystallization of SAA to amyloid fibrils on small beta-sheeted fragments, the 'amyloid enhancing factor' (AEF), is known and the AEF has been shown to penetrate the enteric barrier. Amyloid fibrils can aggregate from various precursor proteins in vitro in particular at acidic pH and when proteolytic fragments are formed. Molecular chaperones influence this process. Tissue data point to amyloid fibrillogenesis in lysosomes and near cell surfaces. A comparison can be made of the fibrillogenesis in prion diseases and in enhanced AA-amyloidosis. In the reactive form, acute phase SAA is the supply of the precursor protein, whereas in the prion diseases, cell membrane proteins form a structural source. Aβ-amyloid in brain tissue of aged dogs showing signs of dementia forms a canine counterpart of senile dementia of the Alzheimer type (ccSDAT) in man. Misfolded proteins remain potential food hazards. Developments concerning prevention of amyloidogenesis and therapy of amyloid deposits are shortly commented.

The Amyloid State of Proteins in Human Diseases

“…In vervet monkeys, spontaneous amyloidosis has been linked to the TTR lle122 allelic variant, which is also a disease-causing mutation in humans (Ueda et al, 2011). AA amyloidosis caused by inflammation or infection does occur in animals (Gruys, 2004). …”

A Concise Review of Amyloidosis in Animals

“…The pathology and pathogenesis of amyloidosis is extremely variable due to the multifarious underlying causes of its various forms in different species of animals. About 20–25 different types of proteins with the ability to aggregate, insolubilize, and deposit in tissue as amyloid have been identified [ 4 , 5 ]. A review of the pathology underlying various protein foldings in domestic animals including amyloidosis is given by Gruys [ 5 ].…”

“…About 20–25 different types of proteins with the ability to aggregate, insolubilize, and deposit in tissue as amyloid have been identified [ 4 , 5 ]. A review of the pathology underlying various protein foldings in domestic animals including amyloidosis is given by Gruys [ 5 ]. In animals, at least eight different amyloid precursors have been described [ 6 ].…”

“…In animals, at least eight different amyloid precursors have been described [ 6 ]. The precursor proteins in amyloid fibrils may be amyloidogenic mutants as in some familial amyloidosis, whereas other precursors are normal wild-type proteins [ 5 , 7 ]. The exact mechanisms through which the proteins are converted into amyloid fibrils in vivo are not well known [ 7 ].…”

“Amyloid” — Historical Aspects

“…Indeed, also in this he was ahead of his time. After more than one hundred years other constituents such as glycosaminoglycans and heparan sulphate [12,13] and chondroitin sulphate -containing proteoglycans [14,15] were identified as additional, albeit minor components of amyloid deposits [16].…”