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

Abstract

 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.