Open AccessMolecular mechanisms mediating the neuroproyective effects of quinacrine and minocycline on cell death induced by the prion protein fragment 90-231 (hPrP90-231)
Author(s) -
Valentina Villa,
Alessandro Corsaro,
Stefano Thellung,
Alessandro Simi,
Mario Nizzari,
Michele Tonelli,
Vito Boido,
Antonio Aceto,
Tullio Florio
Publication year - 2011
Publication title -
journal of biological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.218
H-Index - 6
eISSN - 2284-0230
pISSN - 1826-8838
DOI - 10.4081/jbr.2011.4689
Subject(s) - minocycline , internalization , toxicity , chemistry , cell , programmed cell death , protein kinase a , pharmacology , kinase , biochemistry , biology , apoptosis , antibiotics , organic chemistry
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 PrPSc-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