NR AMXR
AU Zanusso,G.; Vattemi,G.; Ferrari,S.; Tabaton,M.; Pecini,E.; Cavallaro,T.; Tomelleri,G.; Filosto,M.; Tonin,P.; Nardelli,E.; Rizzuto,N.; Monaco,S.
TI Increased expression of the normal cellular isoform of prion protein in inclusion-body myositis, inflammatory myopathies and denervation atrophy
QU Brain Pathology 2001 Apr; 11(2): 182-9
PT journal article
AB The cellular isoform of the prion protein (PrPc) is a glycosylphosphatidylinositol-anchored glycoprotein, normally expressed in neural and non-neural tissues, including skeletal muscle. In transmissible spongiform encephalopathies, or prion diseases, PrPc, which is soluble in nondenaturing detergent and sensitive to proteinase K (PK)-treatment, represents the molecular substrate for the production of a detergent-insoluble and PK-resistant isoform, termed PrPsc. In human prion diseases, PrPsc accumulation occurs only in brain tissues, with the exception of new variant Creutzfeldt-Jakob disease, where PrPsc is also detected in lymphoid tissues. Increased amounts of prion protein expression and deposition have been described in pathological muscle fibers of two human muscle disorders, called sporadic inclusion-body myositis (s-IBM) and hereditary inclusion-body myopathy, but it is unknown whether accumulated prion protein reflects normal PrPc or PrPsc. We investigated the biochemical characteristics of prion protein in normal human muscle, s-IBM, other inflammatory myopathies and denervation atrophy. We report that 1) both the glycoform profile and size of the normal muscle PrPc are different from those of human brain PrPc; 2) in addition to s-IBM, increased PrPc expression is seen in polymyositis, dermatomyositis and neurogenic muscle atrophy, but PrPc glycoforms are unchanged; 3) only the normal PrPc isoform, and not PrPsc, is detected in s-IBM. The present results exclude that s-IBM is a prion disease.
IN Die Autoren fanden Unterschiede zwischen den normalen Prionproteinen in Hirn und Muskelzellen hinsichtlich der Molekularmassen und Glykosilierungsmuster. Außerdem stellten sie bei unveränderter Glykosilierung erhöhte PrPc-Expressionen in Muskelzellen von Patienten mit sporadischer inclusion-body-Myositis, Polymyositis, Dermatomyositis und neurogener Muskelatrophie fest. Die Autoren fanden aber in Muskelzellen von Patienten mit sporadischer inclusion-body-Myositis nur normales zelluläres PrPc. Demnach ist die inclusion-body-Myositis keine Prion-Krankheit, könnte aber durch die Steigerung der PrPc-Expresion im Falle einer zusätzlichen TSE-Infektion zu PrPsc-Akkumulationen in Muskeln führen.
MH Adult; Brain/cytology/*metabolism/pathology; Human; Inflammation; Leukocytes/cytology/metabolism/pathology; Middle Age; Muscle Denervation; Muscle Fibers/metabolism/pathology; Muscle, Skeletal/cytology/*metabolism/*pathology; Muscular Atrophy/*metabolism/pathology; Muscular Diseases/*metabolism/pathology; Myositis, Inclusion Body/*metabolism/pathology; Phosphoprotein Phosphatase/analysis/*metabolism; Reference Values; Support, Non-U.S. Gov't
AD Department of Neurological and Visual Sciences, University of Verona, Italy.
SP englisch
PO Schweiz