P3-237 Degradation of tau - does the proteasomal system play a role?

Keck, Susi; Gräfe, Anja; Ullrich, Oliver; Grune, Tilman

doi:10.1016/s0197-4580(04)81387-3

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“…The third mechanism for reducing tau expression is through perturbation of tau synthesis and/or degradation pathways. Reports have shown that tau protein has a long half-life in cells, indicating that its expression and turnover are tightly coordinated (18, 19). Compounds that disrupt this regulation (such as activating a protease that clears tau) may lower tau levels in neurons.…”

Section: Introductionmentioning

confidence: 99%

A High-Throughput Screening Assay for Determining Cellular Levels of Total Tau Protein

Dehdashti

Zheng²,

Gever³

et al. 2013

CAR

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The microtubule-associated protein (MAP) tau has been implicated in the pathology of numerous neurodegenerative diseases. In the past decade, the hyperphosphorylated and aggregated states of tau protein have been important targets in the drug discovery field for the potential treatment of Alzheimer’s disease. Although several compounds have been reported to reduce the hyperphosphorylated state of tau or impact the stabilization of tau, their therapeutic activities are still to be validated. Recently, reduction of total cellular tau protein has emerged as an alternate intervention point for drug development and a potential treatment of tauopathies. We have developed and optimized a homogenous assay, using the AlphaLISA and HTRF assay technologies, for the quantification of total cellular tau protein levels in the SH-SY5Y neuroblastoma cell line. The signal-to-basal ratios were 375 and 5.3, and the Z’ factors were 0.67 and 0.60 for the AlphaLISA and HTRF tau assays, respectively. The clear advantages of this homogeneous tau assay over conventional total tau assays, such as ELISA and Western blot, are the elimination of plate wash steps and miniaturization of the assay into 1536-well plate format for the ultra–high-throughput screening of large compound libraries.

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Section: Introductionmentioning

confidence: 99%