Academic Journal

In Vitro and In Vivo Neurotoxicity of Prion Protein Oligomers

التفاصيل البيبلوغرافية
العنوان: In Vitro and In Vivo Neurotoxicity of Prion Protein Oligomers
المؤلفون: Steve Simoneau, Human Rezaei, Nicole Salès, Gunnar Kaiser-schulz, Maxime Lefebvre-roque, Catherine Vidal, Jean-guy Fournier, Julien Comte, Franziska Wopfner, Jeanne Grosclaude, Hermann Schätzl, Corinne Ida Lasmézas
المساهمون: The Pennsylvania State University CiteSeerX Archives
المصدر: ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/38/f4/PLoS_Pathog_2007_Aug_31_3(8)_e125.tar.gz
المجموعة: CiteSeerX
الوصف: 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.
نوع الوثيقة: text
وصف الملف: application/zip
اللغة: English
Relation: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.279.2787
الاتاحة: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.279.2787
Rights: Metadata may be used without restrictions as long as the oai identifier remains attached to it.
رقم الانضمام: edsbas.F6324178
قاعدة البيانات: BASE