Anti-LRP/LR specific antibodies and shRNAs impede amyloid beta shedding in Alzheimer's disease

作者：Jovanovic Katarina; Gonsalves Danielle; Dias Bianca Da Costa; Moodley Kiashanee; Reusch Uwe; Knackmuss Stefan; Penny Clement; Weinberg Marc S; Little Melvyn; Weiss Stefan F T^*

来源：Scientific Reports, 2013, 3(1): 2699.

DOI：10.1038/srep02699

Alzheimer's disease (AD) is the most prevalent form of dementia. The amyloid beta (Ab) peptide is the predominant candidate aetiological agent and is generated through the sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by beta (beta) and gamma (gamma) secretases. Since the cellular prion protein (PrPc) has been shown to regulate Ab shedding, we investigated whether the cellular receptor for PrPc, namely the 37 kDa/67 kDa Laminin Receptor (LRP/LR) played a role in Ab shedding. Here we show that LRP/LR co-localises with the AD relevant proteins APP, beta- and c-secretase, respectively. Antibody blockage and shRNA knock-down of LRP/LR reduces Ab shedding, due to impediment of beta-secretase activity, rather than alteration of APP, beta- and gamma-secretase levels. These findings indicate that LRP/LR contributes to Ab shedding and recommend anti-LRP/LR specific antibodies and shRNAs as novel therapeutic tools for AD treatment.

• 出版日期2013-9-19