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

Cuttler, K.; Bignoux, M.; Otgaar, T. C.; Chigumba, S.; Ferreira, E.; Weiss, S. F.

2020-01-15 neuroscience
10.1101/2020.01.14.905661 bioRxiv
Show abstract

Alzheimers disease (AD) is characterized by amyloid beta (A{beta}) 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 A{beta} 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 PrPc 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 Alzheimers Disease and recommend LRP::FLAG as a potential alternative therapeutic tool for Alzheimers Disease treatment through rescuing cells from A{beta} induced cytotoxicity and, as shown in this report, decreased phosphorylated tau levels.

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