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Role of Prion Protein Aggregation in Neurotoxicity
Section of Pharmacology, Department of Internal Medicine, University of Genova, Genova 16132, Italy
* Author to whom correspondence should be addressed.
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 misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126) and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.
Keywords: transmissible spongiform encephalopathies; prion protein aggregation; hPrP90-231 mutants and wild type; cell internalization
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Corsaro, A.; Thellung, S.; Villa, V.; Nizzari, M.; Florio, T. Role of Prion Protein Aggregation in Neurotoxicity. Int. J. Mol. Sci. 2012, 13, 8648-8669.
Corsaro A, Thellung S, Villa V, Nizzari M, Florio T. Role of Prion Protein Aggregation in Neurotoxicity. International Journal of Molecular Sciences. 2012; 13(7):8648-8669.
Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Nizzari, Mario; Florio, Tullio. 2012. "Role of Prion Protein Aggregation in Neurotoxicity." Int. J. Mol. Sci. 13, no. 7: 8648-8669.