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Author Notes:

Correspondence: Xiao-Jiang Li, xli2@emory.edu; Shi-Hua Li, sli@emory.edu

Author contributions: TZ, YH, X-JL and S-HL wrote this review article.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Research Funding:

This work was supported by NIH Grants (AG19206 and NS041449 to X-JL, NS095279 and NS095181 to S-HL).


  • huntingtin
  • neurodegeneration
  • proteasome
  • autophagy
  • aggregation

Subcellular clearance and accumulation of huntington disease protein: A mini-review


Journal Title:

Frontiers in Molecular Neuroscience


Volume 9, Number APR


Type of Work:

Article | Final Publisher PDF


Huntington’s disease (HD) is an autosomal dominant, progressive neurodegenerative disease caused by an expanded polyglutamine (polyQ) tract in the N-terminal region of mutant huntingtin (mHtt). As a result, mHtt forms aggregates that are abundant in the nuclei and processes of neuronal cells. Although the roles of mHtt aggregates are still debated, the formation of aggregates points to deficient clearance of mHtt in brain cells. Since the accumulation of mHtt is a prerequisite for its neurotoxicity, exploring the mechanisms for mHtt accumulation and clearance would advance our understanding of HD pathogenesis and help us develop treatments for HD. We know that the ubiquitinproteasome system (UPS) and autophagy play important roles in clearing mHtt; however, how mHtt preferentially accumulates in neuronal nuclei and processes remains unclear. Studying the clearance of mHtt in neuronal cells is a challenge because neurons are morphologically and functionally polarized, which means the turnover of mHtt may be distinct in different cellular compartments. In this review, we discuss our current knowledge about the clearance and accumulation of mHtt and strategies examining mHtt clearance and accumulation in different subcellular regions.

Copyright information:

© 2016 Zhao, Hong, Li and Li.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

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