LRP::FLAG Rescues Cells from Amyloid-ß-Mediated Cytotoxicity Through Increased TERT Levels and Telomerase Activity.

ABSTRACT

Alzheimer's disease (AD) represents the most common form of neurodegenerative disorders with only palliative treatments currently available. Amyloid plaque formation caused by amyloid-ß (Aß) aggregation and neurofibrillary tangle formation caused by hyperphosphorylated tau are hallmarks for the development of AD. The 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in AD and tools blocking or downregulating LRP/LR impede amyloid plaque formation in vitro and in vivo. We have recently shown that LRPFLAG enhances telomerase activity with a concomitant reduction of senescent markers. Here, we overexpressed LRPFLAG in HEK293 and SH-SY5Y cells, which resulted in an increase in hTERT levels as well as increased telomerase activity and increased cell viability in the presence of cytotoxic levels of exogenous Aß. LRPFLAG overexpression decreased Aß shedding and intracellular Aß levels in HEK293 cells. This suggests that LRPFLAG rescues cells from Aß-induced cytotoxicity through increased telomerase activity. This study recommends LRPFLAG as a novel alternative therapeutic for AD treatment through activation of telomerase activity.