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Author Notes:

Corresponding Author(s): Shihua Li ; Email: sli@emory.edu Xiao-Jiang Li ; Email: xli2@emory.edu Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Room 347, Atlanta, GA 30322, USA

No potential conflicts of interest were disclosed.

Subjects:

Research Funding:

This work is supported by NIH grant NS095279 (to Shihua Li).

Keywords:

  • SCA17
  • TBP
  • polyglutamine
  • transcription

Molecular mechanisms underlying Spinocerebellar Ataxia 17 (SCA17) pathogenesis.

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Journal Title:

Rare Diseases

Volume:

Volume 4, Number 1

Publisher:

, Pages e1223580-e1223580

Type of Work:

Article | Final Publisher PDF

Abstract:

Spinocerebellar ataxia 17 (SCA17) belongs to the family of 9 genetically inherited, late-onset neurodegenerative diseases, which are caused by polyglutamine (polyQ) expansion in different proteins. In SCA17, the polyQ expansion occurs in the TATA box binding protein (TBP), which functions as a general transcription factor. Patients with SCA17 suffer from a broad array of motor and non-motor defects, and their life expectancy is normally within 20 y after the initial appearance of symptoms. Currently there is no effective treatment, but remarkable efforts have been devoted to tackle this devastating disorder. In this review, we will summarize our current knowledge about the molecular mechanisms underlying the pathogenesis of SCA17, with a primary focus on transcriptional dysregulations. We believe that impaired transcriptional activities caused by mutant TBP with polyQ expansion is a major form of toxicity contributing to SCA17 pathogenesis, and rectifying the altered level of downstream transcripts represents a promising therapeutic approach for the treatment of SCA17.

Copyright information:

© 2016 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/).

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