| | |  | | | | Record from Web of Science® | | | | | | |
| NEUROTOXICITY OF A PRION PROTEIN-FRAGMENT |
|
|
| Author(s): FORLONI G, ANGERETTI N, CHIESA R, MONZANI E, SALMONA M, BUGIANI O, TAGLIAVINI F |
| Source: NATURE Volume: 362 Issue: 6420 Pages: 543-546 Published: APR 8 1993 |
| Times Cited: 649 References: 35 |
| Abstract: THE cellular prion protein (PrP(C)) is a sialoglycoprotein of M(r) 33-35K that is expressed predominantly in neurons1-3. In transmissible and genetic neurodegenerative disorders such as scrapie of sheep, spongiform encephalopathy of cattle and Creutzfeldt-Jakob or Gerstmann-Straussler-Scheinker diseases of humans4,5, PrP(C) is converted into an altered form (termed PrP(Sc)) which is distinguishable from its normal homologue by its relative resistance to protease digestion6-8. PrP(Sc) accumulates in the central nervous system of affected individuals8,9 and its protease-resistant core aggregates extracellularly into amyloid fibrils10-12. The process is accompanied by nerve cell loss, whose pathogenesis and molecular basis are not understood. We report here that neuronal death results from chronic exposure of primary rat hippocampal cultures to micromolar concentrations of a peptide corresponding to residues 106-126 of the amino-acid sequence deduced from human PrP complementary DNA. DNA fragmentation of degenerating neurons indicates that cell death occurred by apoptosis. The PrP peptide 106-126 has a high intrinsic ability to polymerize into amyloid-like fibrils in vitro. These findings indicate that cerebral accumulation of PrP(Sc) and its degradation products may play a role in the nerve cell degeneration that occurs in prion-related encephalopathies. |
| Document Type: Article |
| Language: English |
| Reprint Address: FORLONI, G (reprint author), MARIO NEGRI INST PHARMACOL RES, VIA ERITREA 62, I-20157 MILAN, ITALY |
Addresses:
1. IST NAZL NEUROL CARLO BESTA, I-20133 MILAN, ITALY |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: KW453 |
| ISSN: 0028-0836 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |