Bad Boy with a Twist: Targeting the 37 kDa/67 kDa Laminin Receptor for Treatment of Cancer and Neurodegenerative Diseases and for Changing Telomere Dynamics

Not many receptors are as multifunctional as the 37kDa/67kDa laminin receptor (LRP/LR) [1,2]. Is LRP/LR the black sheep, the “bad boy”, the one who promotes cancer, prion disorders, Alzheimer's disease, bacterial, viral and parasite infections? [1,2]. Indeed, LRP/LR, also known as LAMR, ribosomal protein SA (RPSA) or p40, acts as the receptor for the cellular and infectious prion proteins PrPc [3] and PrPSc [4] respectively, and promotes prion propagation in vitro and in vivo, processes which can be impeded by LRP/LR specific antibodies and siRNA mediated knock-down of LRP [5]. In particular, passive immune-transfer of a LRP/LR specific antibody (W3) into Scrapie-infected mice resulted in a significant reduction of the peripheral prion propagation and prolonged survival of the mice [6]. Targeting LRP/LR might therefore be a therapeutic option for human prion disorders such as Creutzfeldt-Jakob Disease. LRP/LR also serves as a receptor for amyloid-beta (A-beta) and promotes A-beta shedding contributing to neurotoxicity in Alzheimer's disease [1]. LRP specific antibodies and shRNAs directed against LRP mRNA were both efficient in impeding A-beta induced cytotoxicity [1,2]. Interestingly, the prion protein PrPc is necessary for the rescuing effect of LRP/LR specific antibodies on A-beta induced cytotoxicity [7]. These findings recommend LRP/LR specific antibodies and siRNAs as alternative powerful therapeutics for Alzheimer's disease.