Properties and Pathogenicity of Prion-Derived Peptides
Prion diseases are neurodegenerative disorders characterized by a hallmark event involving the posttranslational misfolding of the normal cellular prion protein (PrPC) into an infectious and toxic protease-resistant conformation (PrPSc). Studies on identification of the pathological prion species and on the mechanisms involved in triggering neuronal death have been hampered by the heterogeneous nature of PrPSc aggregates. The use of synthetic PrP-derived peptides has made possible exploration of the relationship between amino acid sequence, biophysical structure and biological effect. Indeed, most PrP-derived peptides replicate the fundamental aspects of full-length PrPSc, including: a β- sheet-rich structure; destabilization of lipid membranes; intracellular calcium dysregulation; increased oxidative stress; activation of pro-apoptotic signaling pathways; and, more contentiously, neurotoxicity dependent upon endogenous PrPC expression. Crucially, in vivo toxicity of the important PrP-peptides, e.g. PrP(106-126) and PrP(118-135), has additionally been established. Therefore, the use of prion-derived peptides facilitates the development of therapeutic strategies based on small-molecule inhibitors of aggregation and other pharmacological agents that protect against the lethal effect of these peptides in vivo.
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Document Type: Research Article
Publication date: 2009-03-01
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- Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.