Next Article in Journal
EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts
Next Article in Special Issue
Comparing the Folds of Prions and Other Pathogenic Amyloids
Previous Article in Journal
Soluble CD14 as a Diagnostic Biomarker for Smear-Negative HIV-Associated Tuberculosis
Previous Article in Special Issue
The Structure of PrPSc Prions

Pharmacological Agents Targeting the Cellular Prion Protein

Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy
Dulbecco Telethon Laboratory of Prions and Amyloids, Centre for Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy
Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy
Authors to whom correspondence should be addressed.
Pathogens 2018, 7(1), 27;
Received: 8 February 2018 / Revised: 1 March 2018 / Accepted: 2 March 2018 / Published: 7 March 2018
(This article belongs to the Special Issue PrPSc prions: state of the art)
Prion 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
Keywords: cellular prion protein; prion diseases; PrP ligands; pharmacological chaperones cellular prion protein; prion diseases; PrP ligands; pharmacological chaperones
Show Figures

Figure 1

MDPI and ACS Style

Barreca, M.L.; Iraci, N.; Biggi, S.; Cecchetti, V.; Biasini, E. Pharmacological Agents Targeting the Cellular Prion Protein. Pathogens 2018, 7, 27.

AMA Style

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., Nunzio Iraci, Silvia Biggi, Violetta Cecchetti, and Emiliano Biasini. 2018. "Pharmacological Agents Targeting the Cellular Prion Protein" Pathogens 7, no. 1: 27.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop