Amyloids diseases

Neve, RL and Robakis, NK (1998) Amyloid disease a re-examination of the amyloid hypothesis. Trends Neurosci. 21 15-19. 

Kelly JW (1998) The environmental dependency of protein folding best explains prion and amyloid diseases. Proc Natl Acad Sci USA 95 930-932. 

Amyloid fibrils are elongated, insoluble protein aggregates deposited in vivo in amyloid diseases, and amyloid-like fibrils are formed in vitro from soluble proteins. Both of these groups of fibrils, despite differences in the sequence and native structure of their component proteins, share common... 

The mysterious prions (proteinaceous infective agents), which are described briefly on p. 248, are under intensive investigation. Prion diseases affect fewer than one in 100,000 persons, but there is fear of a possible epidemic. Furthermore, there is a close relationship of prions to a large family of amyloid diseases. The most frequent of these is Alzheimer disease, which is estimated to affect one-third of people over 85 years of age in the United States.3/b... 

Fig. 13.8. Correlation between expression levels and the measured aggregation rates for a set of human proteins. The aggregation rates represent all the data obtained from a comprehensive search of the amyloid aggregation literature, for studies carried out at pH values between 4.0 and 8.0. The expression levels are estimated from the cellular mRNA concentration and are taken from published databases. The standard deviations of the aggregation rates are reported only in four cases, as these values are generally not available or difficult to extract from the literature. Data for two proteins not involved in any known medical conditions are included in the plot while the other points correspond to proteins that are associated with amyloid diseases. From [4]...

The structure shared by amyloid fibrils and the common themes in its assembly provide a unifying mechanism of cell toxicity thus, a better understanding of the amyloid assembly process at the molecular level should give invaluable insight into the identification and the development of effective therapeutic innovations for a wide variety of human amyloid diseases. 

Hammarstrom P, Wiseman RL, Powers ET, Kelly JW. Prevention of transthyretin amyloid disease by changing protein misfolding energetics. Science 2003 299 713-716. 

Lashuel HA, Lansbury PT. Are amyloid disease caused by protein aggregates that mimic bacterial pore-forming toxins Quart. Rev. Biophys. 2006 39 167-201. 

Gazit E. The role of prefibrillar assemblies in the pathogenesis of amyloid diseases. Drugs Put. 2004 29 613-619. 

The amyloidoses are a class of conformational diseases that arise from the conversion of normally unfolded or globular proteins into fibrillar aggregates that are either pathogenic or non-functional. At present there are more than 20 proteins that are associated with human amyloid diseases. This review focuses on three natively unfolded proteins that form fibrillar aggregates amyloid-, islet amyloid polypeptide ( amylin ), and a-synuclein, the diseases they contribute to and chemical and biophysical approaches that are used to investigate these proteins aggregation. 

Modified from Buxbaum JN, Tlie amyloid diseases. In Wyngaarden JB, Smith LH Jr, editors. Cecil Textbook of Medicine. 17th ed. Philadelphia WB Saunders, 1985 1169,... 

Familial Amyloidosis. Several genetically transmitted forms of amyloid disease have been reported. These have primarily neurological but also renal and vascular symptoms (Table 20-14), The fibrils of the Portuguese and Swedish syndromes and the polyneuropathic amyloid syndrome of Ashkenazic Jews have monomers of 14 kDa that share antigenic determinants and amino acid homology with prealbumin (transthyretin). 

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