Molecular mechanisms mediating the neuroproyective effects of quinacrine and minocycline on cell death induced by the prion protein fragment 90-231 (hPrP90-231)

• Main Authors: V. Villa, A. Corsaro, S. Thellung, A. Simi, M. Nizzari, M. Tonelli, V. Boido, A. Aceto, T. Florio
• Format: Article
• Language: English
• Published: PAGEPress Publications 2011-01-01
• Series: Journal of Biological Research
• Subjects: prion protein, quinacrine, minocycline
• Online Access: http://www.pagepressjournals.org/index.php/jbr/article/view/4689
• ISSN: 1826-8838; 2284-0230

The effects of quinacrine and minocycline on the toxicity induced by hPrP90-231 were studied. By mild thermal denaturation, hPrP90-231 can be converted in a toxic PrP^Sc-like structure affecting the survival of SH-SY5Y cells. Quinacrine and minocycline prevented hPrP90-231-induced toxicity interfering with different mechanisms: protective effects of quinacrine are mediated by the binding to the fragment that abolished hPrP90-231 structural changes and cell internalization, whereas, minocycline reverted MAP kinase neurotoxic signaling exerted by the prion fragment.