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 the37kDa/67kDa laminin receptor (LRP/LR) [1,2]. Is LRP/LRthe black sheep, the “bad boy”, the one who promotescancer, prion disorders, Alzheimer’s disease, bacterial,viral and parasite infections? [1,2]. Indeed, LRP/LR, alsoknown as LAMR, ribosomal protein SA (RPSA) or p40, actsas the receptor for the cellular and infectious prionproteins PrPc [3] and PrPSc [4] respectively, andpromotes prion propagation in vitro and in vivo,processes which can be impeded by LRP/LR specificantibodies and siRNA mediated knock-down of LRP [5]. Inparticular, passive immune-transfer of a LRP/LR specificantibody (W3) into Scrapie-infected mice resulted in asignificant reduction of the peripheral prion propagationand prolonged survival of the mice [6]. Targeting LRP/LRmight therefore be a therapeutic option for human priondisorders such as Creutzfeldt-Jakob Disease. LRP/LR alsoserves as a receptor for amyloid-beta (A-beta) andpromotes A-beta shedding contributing to neurotoxicityin Alzheimer’s disease [1]. LRP specific antibodies andshRNAs directed against LRP mRNA were both efficient inimpeding A-beta induced cytotoxicity [1,2]. Interestingly,the prion protein PrPc is necessary for the rescuing effectof LRP/LR specific antibodies on A-beta inducedcytotoxicity [7]. These findings recommend LRP/LRspecific antibodies and siRNAs as alternative powerfultherapeutics for Alzheimer’s disease.