title: In vivo cytotoxicity of the prion protein fragment 106-126.
abstract: Transmissible spongiform encephalopathies are fatal neurological diseases characterized by astroglyosis, neuronal loss, and by the accumulation of the abnormal isoform of the prion protein. The amyloid prion protein fragment 106-126 (P106-126) has been shown to be toxic in cultured hippocampal neurons (). Here, we show that P106-126 is also cytotoxic in vivo. Taking advantage of the fact that retina is an integral part of the central nervous system, the toxic effect of the peptide was investigated by direct intravitreous injection. Aged solutions of P106-126 induced apoptotic-mediated retinal cell death and irreversibly altered the electrical activity of the retina. Neither apoptosis nor electroretinogram damages were observed with freshly diluted P106-126, suggesting that the toxicity is linked to the aggregation state of the peptide. The retina provides a convenient in vivo system to look for potential inhibitors of cytotoxicity associated with spongiform encephalopathies.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Sophia Antipolis, 06560 Valbonne, France.
authors.forename: M
authors.initials: M
authors.lastname: Ettaiche
authors.forename: R
authors.initials: R
authors.lastname: Pichot
authors.forename: J P
authors.initials: JP
authors.lastname: Vincent
authors.forename: J
authors.initials: J
authors.lastname: Chabry
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011328:Prions / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126)