NR ARWJ
AU Tagliavini,F.; McArthur,R.A.; Canciani,B.; Giaccone,G.; Porro,M.; Bugiani,M.; Lievens,P.M.J.; Bugiani,O.; Peri,E.; Dall'Ara,P.; Rocchi,M.; Poli,G.; Forloni,G.; Salmona,M.; Bandiera,T.; Varasi,M.; Suarato,A.; Cassutti,P.; Cervini,M.A.; Lansen,J.; Post,C.
TI Anthracyclines effective against experimental scrapie
QU Journal of Neuropathology and Experimental Neurology 1997; 56(N5): 595 Nr. 97
PT Meeting Abstract
VT Prion diseases are characterised by the accumulation of abnormal isoforms of the prion protein, termed PrPres, in the brain. Unlike the normal PrP, PrPres has a high content of B-sheet secondary structure and a high tendency to aggregate into amyloid fibrils. The observation that the anthracycline iododoxorubicin (IDX) binds to amyloid fibrils and induces amyloid resorption in patients with peripheral amyloidosis prompted us to investigate the effects of this drug on experimental scrapie. Syrian hamsters were inoculated intracerebrally with brain homogenate of hamsters infected with the 263K scrapie strain. In separate groups of animals, the brain homogenate was incubated for 1 hr with 2.9 mM IDX before inoculation. Seven weeks after infection, detailed behavioural observations (including tactile and acoustic reactivity, motor disturbances, and latency to leave an enclosed area) were recorded twice a week in order to detect the onset and the progression of neurological dysfunction. IDX delayed the onset of clinical signs of disease and prolonged the survival time significantly. Neuropathological examination showed a parallel delay in the appearance of spongiosis and astrogliosis as well as in the accumulation of PrPres and PrP amyloid. This was revealed by immunocytochemistry and immunoblot analysis of brain homogenates with anti-PrP antibodies. In the terminal stage of the disease, brain changes and PrPres levels were similar in all groups. These data suggest that IDX is able to interact with abnormal PrP isoforms, interfering with the development of the disease.
IN Das Anthracyclin Iododoxorubicin (IDX) bindet an amyloide Fibrillen. Eine einstündige Inkubation 263K-scrapieinfektiöser Hirnhomogenate vor deren Inokulation in die Gehirne mit 2,9 mM Iododoxorubicin verlängerte signifikant die Inkubationszeit und verzögerte parallel das Auftreten von Spongiosis und Astrogliose, sowie die Akkumulation von proteaseresistentem Prionprotein und PrP-Amyloiden.
AD
Tagliavini,F.1*; McArthur,R.A.2; Canciani,B.1; Giaccone,G.1; Porro,M.1; Bugiani,M.1; Lievens,P.M.J.1; Bugiani,O.1*; Peri,E.3; Dall'Ara,P.3; Rocchi,M.3; Poli,G.3; Forloni,G.4; Salmona,M.4; Bandiera,T.2; Varasi,M.2; Suarato,A.2; Cassutti,P.2; Cervini,M.A.2; Lansen,J.2; Post,C.2
1 Istituto Neurologico Carlo Besta, Milano,
2 Pharmacia & Upjohn, CNS R&D, Nerviano, Milano,
3 Istituto di Microbiologia Veterinaria, Università, Milano,
4 Istituto Mario Negri, Milano, Italy
ZR 0
SP englisch
OR Prion-Krankheiten 8