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Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
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Tau Isoforms: Gaining Insight into MAPT Alternative Splicing.

Andrea Corsi1, Cristina Bombieri1, Maria Teresa Valenti1

  • 1Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.

International Journal of Molecular Sciences
|December 11, 2022
PubMed
Summary

This review explores the regulation of Tau splicing, crucial for neuronal function and implicated in neurodegenerative diseases like Alzheimer's. Understanding Tau isoform expression offers potential for novel RNA-based therapies.

Keywords:
MAPTPTBP1RBPTaualternative splicingtauopathies

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Tau proteins, encoded by the MAPT gene, are vital for neuronal function, including axonal transport and synaptic plasticity.
  • Dysregulation and aggregation of Tau isoforms are hallmarks of neurodegenerative tauopathies such as Alzheimer's disease.

Purpose of the Study:

  • To review recent advancements in understanding Tau isoform expression and its regulatory mechanisms.
  • To highlight experimental models and the role of cis-elements and ribonucleoproteins in Tau splicing.

Main Methods:

  • Literature review of recent contributions to Tau splicing research.
  • Analysis of experimental models for studying Tau expression.
  • Examination of regulatory elements (cis-elements, ribonucleoproteins) involved in alternative splicing.

Main Results:

  • Tau splicing generates six major isoforms with differential expression during neuronal development.
  • Complex regulatory mechanisms involving cis-elements and ribonucleoproteins control Tau alternative splicing.
  • Alterations in Tau splicing are linked to the pathogenesis of major tauopathies.

Conclusions:

  • Understanding Tau splicing regulation is key to deciphering neurodegenerative disease mechanisms.
  • Targeting Tau splicing pathways presents a promising avenue for developing RNA-based therapeutic strategies for tauopathies.