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Unraveling Prion Protein Interactions with Aptamers and Other PrP-Binding Nucleic Acids
- Source :
- International Journal of Molecular Sciences
- Publication Year :
- 2017
- Publisher :
- MDPI, 2017.
-
Abstract
- Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative disorders that affect humans and other mammals. The etiologic agents common to these diseases are misfolded conformations of the prion protein (PrP). The molecular mechanisms that trigger the structural conversion of the normal cellular PrP (PrPC) into the pathogenic conformer (PrPSc) are still poorly understood. It is proposed that a molecular cofactor would act as a catalyst, lowering the activation energy of the conversion process, therefore favoring the transition of PrPC to PrPSc. Several in vitro studies have described physical interactions between PrP and different classes of molecules, which might play a role in either PrP physiology or pathology. Among these molecules, nucleic acids (NAs) are highlighted as potential PrP molecular partners. In this context, the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology has proven extremely valuable to investigate PrP–NA interactions, due to its ability to select small nucleic acids, also termed aptamers, that bind PrP with high affinity and specificity. Aptamers are single-stranded DNA or RNA oligonucleotides that can be folded into a wide range of structures (from harpins to G-quadruplexes). They are selected from a nucleic acid pool containing a large number (1014–1016) of random sequences of the same size (~20–100 bases). Aptamers stand out because of their potential ability to bind with different affinities to distinct conformations of the same protein target. Therefore, the identification of high-affinity and selective PrP ligands may aid the development of new therapies and diagnostic tools for TSEs. This review will focus on the selection of aptamers targeted against either full-length or truncated forms of PrP, discussing the implications that result from interactions of PrP with NAs, and their potential advances in the studies of prions. We will also provide a critical evaluation, assuming the advantages and drawbacks of the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technique in the general field of amyloidogenic proteins.
- Subjects :
- 0301 basic medicine
Aptamer
animal diseases
aptamers
DNA, Single-Stranded
Context (language use)
Amyloidogenic Proteins
Computational biology
Review
Biology
Catalysis
Prion Proteins
Prion Diseases
Inorganic Chemistry
03 medical and health sciences
chemistry.chemical_compound
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
Spectroscopy
Oligonucleotide
Organic Chemistry
SELEX Aptamer Technique
RNA
General Medicine
Aptamers, Nucleotide
Molecular biology
In vitro
Computer Science Applications
nervous system diseases
SELEX (Systematic Evolution of Ligands by Exponential Enrichment)
nucleic acids
030104 developmental biology
chemistry
prion protein
Nucleic acid
Carrier Proteins
Systematic evolution of ligands by exponential enrichment
DNA
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 18
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....e002519a8e02778f8e13c6cfde5372cf