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Prion diseases are characterized by neurodegeneration and protein aggregation,which are caused by the accumulation of a misfolded and protease-resistant form of the cellular prion protein.Several studies suggest that the accumulation of a misfolded altate cellular protein disturbs quality control mechanisms,leading to endoplasmic reticulum (ER) stress involved in prion diseases[1-3].Prion infection activates the splicing of the unfolded protein response transcription factor XBP-1.Misfolded mutant PrP associated with inherited accumulation in the ER may also affect the activity of proteins controlling the influx/efflux of calcium and decrease ER calcium content[1-4].These events may alter cellular protein folding and quality control mechanisms to generate ER stress.Under cellular stress,cap-dependent translation is inhibited.On the other hand,protein translation is regulated by an intal ribosome entry site (IRES)-mediated cap-independent mechanism.Thus,prion infection may induce IRES-mediated cap-independent initiation of translation.Up-regulation of 14-3-3 proteins,which regulate multiple pivotal points in the cellular life cycle,are found in cerebrospinal fluid prion diseases,as well as being abundant in the brain[5-15].This implies that 14-3-3 cap-independent initiation translation may be induced by ER stress during prion infection.