LRP/LR as an Alternative Promising Target in Therapy of Prion Diseases, Alzheimers Disease and Cancer

Karen      Vana; Chantal      Zuber; Heike      Pflanz; Dominika      Kolodziejczak; Georgeta      Zemora; Ann-Katrin      Bergmann; Stefan      Weiss

Abstract

The 37 kDa/67 kDa laminin receptor (LRP/LR) represents a key player for cell adhesion, is associated with the metastatic potential of solid tumors and is required for maintenance of cell viability by preventing apoptosis. LRP/LR acts as a receptor for viruses such as Sindbis virus, Venezuelean Equine Encephalitis (VEE) virus, Adeno-associated-viruses (AAV) and Dengue Virus, the latter causing 50 to 100 million infections in humans per year. LRP/LR acts further as a receptor for prions and represents a multifunctional protein subcellularly located to the nucleus, the cytoplasm and the cell surface. The receptor represents an alternative target for therapy of viral infections, cancer and prion disorders and might play additional roles in further neurodegenerative diseases such as Alzheimers disease. The species barrier in prion disorders might be at least in part determined by the presence of LRP/LR in enterocytes of the intestinal epithelium. Anti- LRP/LR antibodies, siRNAs directed against LRP mRNA, polysulfated glycanes such as pentosan polysulfate and heparan mimetics and LRP decoy mutants are promising tools for blocking or downregulating the receptor and may represent alternative therapeutics for the treatment of prion disorders, Alzheimers Disease and metastatic cancer.

Keywords: 37kDa/67kDa laminin receptor LRP/LR, prion, protein, PrP, neurodegenerative disease, HSPG, pentosan polysulfate, antibody, siRNA, species barrier