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Related Experiment Videos

Identification of tau stem loop RNA stabilizers.

Christine P Donahue1, Jake Ni, Eriks Rozners

  • 1Center for Neurologic Diseases, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Journal of Biomolecular Screening
|May 26, 2007
PubMed
Summary
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Researchers screened 110,000 compounds to find drugs that stabilize the tau stem loop RNA, potentially reducing 4R tau mRNA and treating neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Drug Discovery

Background:

  • Alternative splicing of tau exon 10 generates 3R and 4R tau isoforms.
  • An imbalance in 4R to 3R tau ratio contributes to neurodegenerative diseases like Alzheimer's.
  • The tau RNA stem loop structure influences this ratio, with decreased stability linked to increased 4R tau expression.

Purpose of the Study:

  • To identify small molecules that bind and stabilize the tau stem loop RNA.
  • To develop assays for screening compounds that modulate tau splicing.
  • To explore potential therapeutic strategies for tauopathies.

Main Methods:

  • Developed a high-throughput fluorescent binding assay to screen ~110,000 compounds for tau stem loop binding.
  • Created a fluorescent RNA probe assay to evaluate the stabilizing effects of candidate drugs on the tau stem loop.

Related Experiment Videos

  • Utilized in vitro assays to assess drug-target interactions.

    • Main Results:

    • Successfully screened a large compound library to identify potential binders of the tau stem loop.
    • Developed and validated fluorescent assays for RNA secondary structure interaction screening.
    • Demonstrated the feasibility of using these assays for drug discovery targeting mRNA structures.

    Conclusions:

    • Identified candidate small molecules that bind the tau stem loop in vitro.
    • Established robust assays applicable to identifying molecules interacting with mRNA secondary structures.
    • These findings offer a novel approach for developing therapeutics for neurodegenerative diseases by modulating tau splicing.