[Frontiers in Bioscience 15, 1150-1163, June 1, 2010]

Interactions between PrPc and other ligands with the 37-kDa/67-kDa laminin receptor

Vusi Mbazima, Bianca Da Costa Dias, Aadilah Omar, Katarina Jovanovic, Stefan F T Weiss

School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, Republic of South Africa (RSA)

TABLE OF CONTENTS

1. Abstract
2. The 37-kDa/67-kDa LRP/LR reveals a multifunctional protein
3. The 37-kDa/67-kDa LRP/LR and its influence on prion and zoonotic diseases
4. The role of prion proteins and the 37-kDa/67-kDa LRP/LR in signal transduction and cell cycle
5. Employing antibodies directed against 37-kDa/67-kDa LRP/LR as therapeutic tools for prion diseases
6. Pentosan polysulfate in the treatment of prion diseases
7. Therapeutic interventions utilizing RNA interference for prion disease treatment
8. LRP102-295 mutant as a decoy receptor for the treatment of prion disorders
9. Other strategies for prion disease therapy
10. The role of the prion protein and its receptor in other neurodegenerative diseases
11. 37-kDa/67-kDa LRP/LR and cancer
12. 37-kDa/67-kDa LRP/LR and Viral Diseases
13. Perspective
14. Acknowledgements
15. References

1. ABSTRACT

The 37-kDa/67 kDa laminin receptor (LRP/LR) represents a multifunctional protein. It is a receptor for viruses such as Dengue viruses, Alphaviruses and Adeno-associated viruses (AAV), as well as the cellular prion protein (PrPc) and infectious prions. Furthermore, the 37-kDa/67-kDa LRP/LR plays fundamental roles in basic cell biological processes such as cell adhesion and cell growth and acts as a key player in metastatic cancer, affecting invasion, adhesion and apoptotic processes. This review gives fundamental insights into basic cellular processes affected by LRP/LR including signal transduction and cell cycle progression and focuses on pathophysiological implications of the interaction of prion proteins, laminin, viruses and other ligands with LRP/LR affecting the development of highly-prevalent diseases such as cancer, neurodegenerative diseases such as prion disorders and Alzheimer's disease as well as viral infections. Molecular tools such as LRP/LR specific antibodies and siRNAs targeting LRP expression as possible alternative therapeutics for the treatment of neurodegenerative diseases, metastatic cancer and viral infections are emphasized.