Abstract
The amyloidoses comprise a heterogeneous group of diseases in which 1 out of more than 25 human proteins aggregates into characteristic beta-sheet fibrils with some unique properties. Aggregation is nucleation dependent. Among the known amyloid-forming constituents is the prion protein, well known for its ability to transmit misfolding and disease from one individual to another. There is increasing evidence that other amyloid forms also may be transmissible but only if certain prerequisites are fulfilled. One of these forms is systemic AA-amyloidosis in which an acute-phase reactant, serum AA, is over-expressed and, possibly after cleavage, aggregates into amyloid fibrils, causing disease. In a mouse model, this disorder can easily be transmitted from one animal to another both by intravenous and oral routes. Also, synthetic amyloid-like fibrils made from defined small peptides have this property, indicating a prion-like transmission mechanism. Even some fibrils occurring in the environment can transmit AA-amyloidosis in the murine model. AA-amyloidosis is particularly common in certain areas of Papua New Guinea, probably due to the endemicity of malaria and perhaps genetic predisposition. Now, when kuru is disappearing, more interest should be focused on the potentially lethal systemic AA-amyloidosis.
Highlights
It has been increasingly acknowledged that misfolding and aggregation of proteins into what we call amyloid is a very common phenomenon and associated with several different disorders
MIT, Cambridge, MA, we have studied the effects of amyloid-like fibrils, made from non-natural short peptides intended for nano-technology, and found that these can speed up the development of AA-amyloidosis in the same system
We have found that islet amyloidosis is seedable in vivo by injection of a trace amount of preformed fibrils made of synthetic islet amyloid polypeptide (IAPP) into transgenic mice that express human IAPP
Summary
It has been increasingly acknowledged that misfolding and aggregation of proteins into what we call amyloid is a very common phenomenon and associated with several different disorders. Amyloid is a generic name for in vivo formed fibrillar deposits, characteristic of a number of diseases and which have in common misfolding of a protein with a high degree of betastructure and which aggregate into typical fibrils of undetermined length. Amyloid is a heterogeneous substance and in humans more than 25 different proteins are known to occur in this form, each typical of one or a few clinical conditions (Westermark et al 2007). The local forms are most common and often found in the central nervous system, the cardiovascular system or in some endocrine organs
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