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Translation initiation of the human tau mRNA through an internal ribosomal entry site

Bethany L Veo1, Les A Krushel

  • 1Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.

Journal of Alzheimer'S Disease : JAD
|February 18, 2009
PubMed

Insights

Researchers discovered an internal ribosomal entry site (IRES) in human tau mRNA, suggesting a new way to control tau protein levels. Targeting this tau IRES could offer a novel therapeutic strategy for Alzheimer's disease (AD) and other tauopathies.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Neurofibrillary tangles, a hallmark of Alzheimer's disease (AD), result from tau protein hyperphosphorylation.
  • Reducing tau protein levels in mouse models of AD alleviates disease severity and progression.

Purpose of the Study:

  • To investigate the role of internal ribosomal entry sites (IRES) in the translation of human tau mRNA.
  • To identify novel therapeutic targets for regulating tau expression in AD and related tauopathies.

Main Methods:

  • Analysis of the 5' leader sequence of human tau mRNA.
  • Experimental validation of IRES-dependent translation of tau protein.

Main Results:

  • The 5' leader of human tau mRNA possesses an internal ribosomal entry site (IRES).
  • IRES-dependent translation significantly contributes to tau protein synthesis.

Conclusions:

  • Tau IRES-dependent translation is a key mechanism in tau protein production.
  • Targeting the tau IRES presents a novel therapeutic strategy for Alzheimer's disease and other tauopathies.

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