Pharmacological Agents Targeting the Cellular Prion Protein
AbstractPrion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates in brain tissues of affected individuals. PrPSc is a self-catalytic protein assembly capable of recruiting native conformers of PrPC, and causing their rearrangement into new PrPSc molecules. Several previous attempts to identify therapeutic agents against prion diseases have targeted PrPSc, and a number of compounds have shown potent anti-prion effects in experimental models. Unfortunately, so far, none of these molecules has successfully been translated into effective therapies for prion diseases. Moreover, mounting evidence suggests that PrPSc might be a difficult pharmacological target because of its poorly defined structure, heterogeneous composition, and ability to generate different structural conformers (known as prion strains) that can elude pharmacological intervention. In the last decade, a less intuitive strategy to overcome all these problems has emerged: targeting PrPC, the common substrate of any prion strain replication. This alternative approach possesses several technical and theoretical advantages, including the possibility of providing therapeutic effects also for other neurodegenerative disorders, based on recent observations indicating a role for PrPC in delivering neurotoxic signals of different misfolded proteins. Here, we provide an overview of compounds claimed to exert anti-prion effects by directly binding to PrPC, discussing pharmacological properties and therapeutic potentials of each chemical class. View Full-Text
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Barreca, M.L.; Iraci, N.; Biggi, S.; Cecchetti, V.; Biasini, E. Pharmacological Agents Targeting the Cellular Prion Protein. Pathogens 2018, 7, 27.
Barreca ML, Iraci N, Biggi S, Cecchetti V, Biasini E. Pharmacological Agents Targeting the Cellular Prion Protein. Pathogens. 2018; 7(1):27.Chicago/Turabian Style
Barreca, Maria L.; Iraci, Nunzio; Biggi, Silvia; Cecchetti, Violetta; Biasini, Emiliano. 2018. "Pharmacological Agents Targeting the Cellular Prion Protein." Pathogens 7, no. 1: 27.
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