role of prion protein aggregation in neurotoxicity朊蛋白聚合在神经毒性中的作用.pdfVIP

Int. J. Mol. Sci. 2012, 13, 8648-8669; doi:10.3390/ijm OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review Role of Prion Protein Aggregation in Neurotoxicity Alessandro Corsaro, Stefano Thellung, Valentina Villa, Mario Nizzari and Tullio Florio * Section of Pharmacology, Department of Internal Medicine, University of Genova, Genova 16132, Italy; E-Mails: 606015@unige.it (A.C.); stefano.thellung@unige.it (S.T.); valentina.villa@unige.it (V.V.); mario.nizzari@unige.it (M.N.) * Author to whom correspondence should be addressed; E-Mail: tullio.florio@unige.it; Tel./Fax: +39-10-353-8806. Received: 21 May 2012; in revised form: 29 June 2012 / Accepted: 2 July 2012 / Published: 11 July 2012 Abstract: In several neurodegenerative diseases, such as Parkinson, Alzheimer’s, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP), the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of