In Vitro and In Vivo Neurotoxicity of Prion Protein Oligomers

The mechanisms underlying prion-linked neurodegeneration remain to be elucidated, despite several recent advances in this field. Herein, we show that soluble, low molecular weight oligomers of the full-length prion protein (PrP), which possess characteristics of PrP to PrPsc conversion intermediates such as partial protease resistance, are neurotoxic in vitro on primary cultures of neurons and in vivo after subcortical stereotaxic injection. Monomeric PrP was not toxic. Insoluble, fibrillar forms of PrP exhibited no toxicity in vitro and were less toxic than their oligomeric counterparts in vivo. The toxicity was independent of PrP expression in the neurons both in vitro and in vivo for the PrP oligomers and in vivo for the PrP fibrils. Rescue experiments with antibodies showed that the exposure of the hydrophobic stretch of PrP at the oligomeric surface was necessary for toxicity. This study identifies toxic PrP species in vivo. It shows that PrP-induced neurodegeneration shares common mechanisms with other brain amyloidoses like Alzheimer disease and opens new avenues for neuroprotective intervention strategies of prion diseases targeting PrP oligomers

« Les OGM face aux nouveaux paradigmes de la biologie »

The assessment and risk management of GMOs are inherited from the paradigm of molecular biology born in the 1960s and from theories of evolutionary biology dominant in the years that saw the onset of GMOs. But these paradigms have been greatly challenged by recent advances in these disciplines : the dissolution of the concept of gene, the identification of epigenetic phenomena transmitted hereditarily, the discovery of the new continent of microRNAs, the metapopulation theory, the ability to trace gene flow over long distances, imply otherwise consider the properties of a genetically modified organism, whether or not dedicated to the dispersion in the environment. A symposium organized last february in Paris, in the framework of the ANR GMOs was designed to take the measure of these transformations of the paradigms of biology and to let clear how these results force to rethink the impacts of GMOs in the light of the new biology

Characterization of seven monoclonal antibodies directed against Nicotiana plumbaginifolia ribulose 1,5-bisphosphate carboxylase/oxygenase

International audienc

Etudes cliniques récentes démontrant l'efficacité des glitazones dans le diabète de type 2 et dans d'autres pathologies hors amm

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Identification of the RNA-binding, dimerization, and eIF4GI-binding domains of rotavirus nonstructural protein NSP3

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Production and characterization of specific bovine plasminogen monoclonal antibodies

International audienc

Monoclonal antibodies as probes for the changes in antigenicity of bovine and porcine aspartyl proteases with pH

International audienc

Differential titration of plasmin and plasminogen in milk using sandwich ELISA with monoclonal antibodies

International audienc

Production and characterization of specific bovine plasminogen monoclonal antibodies

International audienc

Differential titration of plasmin and plasminogen in milk using sandwich ELISA with monoclonal antibodies

International audienc