NR AECK
AU Forloni,G.; Del Bo,R.; Angeretti,N.; Chiesa,R.; Smiroldo,S.; Doni,R.; Ghibaudi,E.; Salmona,M.; Porro,M.; Verga,L.; Giaccone,G.; Bugiani,O.; Tagliavini,F.
TI A neurotoxic prion protein fragment induces rat astroglial proliferation and hypertrophy
QU European Journal of Neuroscience 1994 Sep 1; 6(9): 1415-22
PT journal article
AB Prion-related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrPsc) and the deposition of PrP amyloid in the brain. This process is accompanied by neuronal loss and astrogliosis. We recently showed that a synthetic peptide corresponding to residues 106-126 of human PrP is amyloidogenic and causes neuronal death by apoptosis in vitro. In the present study we investigated the effects of 1- and 14-day exposures of rat astroglial cultures to micromolar concentrations of this peptide as well as peptides homologous to other portions of PrP, a peptide corresponding to residues 25-35 of amyloid-beta protein, and a scrambled sequence of PrP 106-126. No significant changes were observed after 1-day exposure of cultures to any peptide. Conversely, 14-day treatment with PrP 106-126 (50 microM) resulted in a 5-fold increase in glial fibrillary acidic protein (GFAP) expression, as evaluated by Northern and Western blot analyses, and a 1.5-fold increment in cell number. Light and electron microscopy immunohistochemistry showed an enlargement in size and density of astroglial processes, and an increase in GFAP-immunoreactive intermediate filaments. These changes were not observed after 14-day treatment of cultures with the other peptides, including PrP 106-126 scrambled. The increase in GFAP expression of astroglial cultures exposed to PrP 106-126 was quantitatively similar to that found in scrapie-infected hamster brains. These results suggest that the PrP region corresponding to residues 106 - 126 is biologically active, and that cerebral accumulation of peptides including this sequence might be responsible for both the neuronal degeneration and the astrogliosis that occur in prion-related encephalopathies.
IN Ein den Aminosäuren 106-126 des menschlichen Prionproteins entsprechendes synthetisches Peptid bewirkt in einer Konzentrationen von 50 µM in Rattenastrogliazellkulturen schon nach 2 Wochen eine 1,5-fache Zunahme der Zellen, eine Zunahme ihrer Ausläufer in Größe und Zahl und eine 5-fache Zunahme der Expression des glialen fibrillären sauren Proteins GFAP.
ZR 47
MH Amino Acid Sequence; Animal; Astrocytes/*cytology/drug effects/metabolism; Cell Division/drug effects; Glial Fibrillary Acidic Protein/metabolism; Hypertrophy; Molecular Sequence Data; Neurotoxins/*pharmacology; Peptide Fragments/*pharmacology; Prions/chemistry/*pharmacology; Rats; Support, Non-U.S. Gov't
AD Alzheimer Neurobiology Unit, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
SP englisch
PO England