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In vitro aggregation assays using hyperphosphorylated tau protein.

Dexin Sui1, Mengyu Liu1, Min-Hao Kuo2

  • 1Department of Biochemistry and Molecular Biology, Michigan State University.

Journal of Visualized Experiments : Jove
|January 16, 2015
PubMed
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Researchers developed new assays using hyperphosphorylated tau to find Alzheimer's disease and tauopathy therapeutics. These high-throughput screens can identify compounds targeting abnormal tau protein aggregation.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Alzheimer's disease and other tauopathies involve neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein.
  • NFT density correlates with cognitive decline, highlighting the need for tau-targeting therapies.
  • Current tau aggregation assays lack pathology-relevant phosphorylation, limiting therapeutic discovery.

Purpose of the Study:

  • To develop novel assays for studying hyperphosphorylated tau aggregation.
  • To enable high-throughput screening for compounds modulating hyperphosphorylated tau kinetics and stability.

Main Methods:

  • Development of two assays utilizing recombinant, hyperphosphorylated tau.
  • Adaptation of assays for scalability in high-throughput screening.

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Main Results:

  • Successful establishment of assays using hyperphosphorylated tau.
  • Demonstrated potential for screening compounds affecting tau aggregate stability and kinetics.

Conclusions:

  • These assays provide a valuable tool for discovering novel therapeutics for Alzheimer's disease and tauopathies.
  • Utilizing hyperphosphorylated tau isoforms in assays is crucial for identifying effective treatments.