Excitotoxicity Through NMDA Receptors Mediates Cerebellar Granule Neuron Apoptosis Induced by Prion Protein 90-231 Fragment (Articolo in rivista)

Type
Label
  • Excitotoxicity Through NMDA Receptors Mediates Cerebellar Granule Neuron Apoptosis Induced by Prion Protein 90-231 Fragment (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1007/s12640-012-9340-9 (literal)
Alternative label
  • Thellung S; Gatta E; Pellistri F; Corsaro A; Villa V; Vassalli M; Robello M; Florio T (2013)
    Excitotoxicity Through NMDA Receptors Mediates Cerebellar Granule Neuron Apoptosis Induced by Prion Protein 90-231 Fragment
    in Neurotoxicity resarch; Springer, New York (Stati Uniti d'America)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Thellung S; Gatta E; Pellistri F; Corsaro A; Villa V; Vassalli M; Robello M; Florio T (literal)
Pagina inizio
  • 301 (literal)
Pagina fine
  • 314 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://link.springer.com/article/10.1007%2Fs12640-012-9340-9 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 23 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 4 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Univ Genoa, Dept Internal Med, Pharmacol Sect, I-16132 Genoa, Italy; Univ Genoa, Ctr Excellence Biomed Res CEBR, Sch Med, I-16132 Genoa, Italy; Univ Genoa, Dept Phys, I-16132 Genoa, Italy; Natl Council Res CNR, Inst Biophys IBF, Genoa, Italy (literal)
Titolo
  • Excitotoxicity Through NMDA Receptors Mediates Cerebellar Granule Neuron Apoptosis Induced by Prion Protein 90-231 Fragment (literal)
Abstract
  • Prion diseases recognize, as a unique molecular trait, the misfolding of CNS-enriched prion protein (PrPC) into an aberrant isoform (PrPSc). In this work, we characterize the in vitro toxicity of amino-terminally truncated recombinant PrP fragment (amino acids 90-231, PrP90-231), on rat cerebellar granule neurons (CGN), focusing on glutamatergic receptor activation and Ca2+ homeostasis impairment. This recombinant fragment assumes a toxic conformation (PrP90-231TOX) after controlled thermal denaturation (1 h at 53 °C) acquiring structural characteristics identified in PrPSc (enrichment in ?-structures, increased hydrophobicity, partial resistance to proteinase K, and aggregation in amyloid fibrils). By annexin-V binding assay, and evaluation of the percentage of fragmented and condensed nuclei, we show that treatment with PrP90-231TOX, used in pre-fibrillar aggregation state, induces CGN apoptosis. This effect was associated with a delayed, but sustained elevation of [Ca2+]i. Both CGN apoptosis and [Ca2+]i increase were not observed using PrP90-231 in PrPC-like conformation. PrP90-231TOX effects were significantly reduced in the presence of ionotropic glutamate receptor antagonists. In particular, CGN apoptosis and [Ca2+]i increase were largely reduced, although not fully abolished, by pre-treatment with the NMDA antagonists APV and memantine, while the AMPA antagonist CNQX produced a lower, although still significant, effect. In conclusion, we report that CGN apoptosis induced by PrP90-231TOX correlates with a sustained elevation of [Ca2+]i mediated by the activation of NMDA and AMPA receptors. (literal)
Editore
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Prodotto
Autore CNR di
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Editore di
Insieme di parole chiave di
data.CNR.it