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

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.