Affiliations: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, South Africa
Correspondence:
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Correspondence to: Stefan F.T. Weiss, School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, South Africa. E-mail: [email protected].
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-β (Aβ) 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 LRP::FLAG enhances telomerase activity with a concomitant reduction of senescent markers. Here, we overexpressed LRP::FLAG 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 Aβ. LRP::FLAG overexpression decreased Aβ shedding and intracellular Aβ levels in HEK293 cells. This suggests that LRP::FLAG rescues cells from Aβ-induced cytotoxicity through increased telomerase activity. This study recommends LRP::FLAG as a novel alternative therapeutic for AD treatment through activation of telomerase activity.
