LRP::FLAG reduces phosphorylated tau levels in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaque and neurofibrillary tangle formation, respectively. Neurofibrillary tangles form as a result of the intracellular accumulation of hyperphosphorylated tau. Telomerase activity and levels of the human reverse transcriptase (hTERT) subunit of telomerase are significantly decreased in AD. Recently it has been demonstrated that the 37kDa/67kDa laminin receptor (LRP/LR) interacts with telomerase and is implicated in Aβ pathology. Here we show that LRP/LR co-localizes with tau in the perinuclear cell compartment and FRET confirmed a direct interaction between LRP/LR and tau in HEK-293 cells. Overexpression of LRP::FLAG in HEK-293 and SH-SY5Y cells decreased total and phosphorylated tau levels with a concomitant decrease in PrP c levels, a tauopathy-related protein. Additionally, LRP::FLAG overexpression resulted in increased hTERT levels. These data indicate for the first time a role of LRP/LR in tauopathy of Alzheimer's Disease and recommend LRP::FLAG as a potential alternative therapeutic tool for Alzheimer's Disease treatment through rescuing cells from A induced cytotoxicity and, as shown in this report, decreased phosphorylated tau levels.

Knock-Down of LRP/LR Influences Signalling Pathways in Late Stage Colorectal Carcinoma Cells

“…microtubules, resulting in functional protein synthesis [6]. In addition to these physiological roles, LRP/LR has also been shown to have pathological roles in several diseases including micro-organism infections [7], Transmissible Spongiform Encephalopathies (TSEs) [8], prion disorders [9], Alzheimer's Disease (AD) [10][11][12][13] and age-related disorders [14]. The receptor has also been shown to play a major role in cancer since it is often overexpressed on the surface of several cancer cells [15][16][17][18][19].…”