[Frontiers in Bioscience 15, 132-150, January 1, 2010]

PrP interactions with nucleic acids and glycosaminoglycans in function and disease

Jerson L. Silva1, Mariana P. B. Gomes1, Tuane C. R. G. Vieira1,Yraima Cordeiro2

1Instituto de Bioquímica Medica, Centro Nacional de Ressonancia Magnetica Nuclear Jiri Jonas, Instituto Nacional de Ciencia e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, CCS, RJ 21941-590, Rio de Janeiro, Brazil, 2Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, RJ 21941-590, Rio de Janeiro, Brazil

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Prion Diseases
2.2. Cellular Prion Protein
2.3. The prion scrapie (PrPSc) and the conversion reaction
3. Are cofactors needed for prion infectivity?
4. Interaction with sulfated polysaccharides
4.1. The paradoxical effect of sulfated glycans.
4.2. The function of the PrPC/GAG interaction
4.3. Heparin/Heparan sulfate binding sites
5. PrP interaction with nucleic acids
5.1. Outline: a decade of interesting findings
5.1.1. DNA
5.1.2. RNA
5.1.3. New insights on RNA structure and function
5.2. DNA vs. RNA: Similarities and differences
5.3. NA chaperone and PrPSc generation
6. Perspectives in therapy and diagnosis
7. Conclusions and Perspectives
8. Acknowledgments
9. References

1. ABSTRACT

Since the first description of prion diseases, great effort has been made toward comprehending this new paradigm in biology. Despite large advances in the field, many questions remain unanswered, especially concerning the conversion of PrPC into PrPSc. How this conformational transition evolves is a crucial problem that must be solved in order to attain further progress in therapeutics and prevention. Recent developments have indicated the requirement for partners of the prion protein in triggering the conversion. In the present review, we will explore the interaction of PrP with some of its most intriguing partners, such as sulfated glycans and nucleic acids. These molecules seem to play a dual role in prion biology and could be fundamental to explaining how prion diseases arise, as well as in the development of effective therapeutic approaches.