NR AXYQ
AU Westermark,P.
TI Transmission of AA-amyloidosis: Similarities with Prion Disorders
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC4.3
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB The systemic amyloidoses are characterized by widely spread amyloid deposits that can affect virtually every organ in the body. The precursor protein, which varies between different forms is produced at one or several locations, circulates with the plasma and is finally deposited as fibrils in the target organs by mechanisms yet to be determined. In one of the more common forms, systemic AA-amyloidosis, the substrate protein serum AA (SAA) is an acute phase reactant, with significant production only when certain proinflammatory signal substances are upregulated. A persistently high plasma concentration of SAA is a prerequisite for AA-amyloidosis to develop. AA-amyloidosis can easily be induced in many strains of mice by an inflammatory challenge, typically after a long lag phase. This phase is dramatically shortened by administration of amyloid fibrils extracted from an amyloidotic mouse, given intravenously, intra-nasally or given in the drinking water. The fibrillar extract is very potent, active down to pg of protein and facilitates amyloid formation even when given several months before an inflammation is induced. Also amyloid-like fibrils, produced in vitro from synthetic peptides have a clear effect, supporting the idea that the active principle is the misfolded and aggregated protein. AA-amyloidosis occurs in many avian and mammalian species. AA-fibrils from some, but not all species seed murine amyloidosis, showing a species barrier. AA-amyloidosis occurs in species, used as human food and may therefore be a risk factor. Consequently, AA-amyloidosis has similarity with prionoses, differing by the need of an upregulated production of the substrate SAA.
AD P. Westermark, Rudbeck laboratory, Department of Genetics and Pathology, Sweden
SP englisch
PO Schottland