Subcellular clearance and accumulation of Huntington disease protein: A mini-review
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. Althou...
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doaj-264b5e752f994d40b89f555bdb5bf3302020-11-24T20:53:45ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992016-04-01910.3389/fnmol.2016.00027194558Subcellular clearance and accumulation of Huntington disease protein: A mini-reviewTing eZhao0Yan eHong1Xiao-Jiang eLi2Shihua eLi3Emory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University School of MedicineHuntington’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 ubiquitin-proteasome system 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 of examining mHtt clearance and accumulation in different subcellular regionshttp://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00027/fullAutophagyAggregationHuntingtinneurodegenerationProteasome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ting eZhao Yan eHong Xiao-Jiang eLi Shihua eLi |
spellingShingle |
Ting eZhao Yan eHong Xiao-Jiang eLi Shihua eLi Subcellular clearance and accumulation of Huntington disease protein: A mini-review Frontiers in Molecular Neuroscience Autophagy Aggregation Huntingtin neurodegeneration Proteasome |
author_facet |
Ting eZhao Yan eHong Xiao-Jiang eLi Shihua eLi |
author_sort |
Ting eZhao |
title |
Subcellular clearance and accumulation of Huntington disease protein: A mini-review |
title_short |
Subcellular clearance and accumulation of Huntington disease protein: A mini-review |
title_full |
Subcellular clearance and accumulation of Huntington disease protein: A mini-review |
title_fullStr |
Subcellular clearance and accumulation of Huntington disease protein: A mini-review |
title_full_unstemmed |
Subcellular clearance and accumulation of Huntington disease protein: A mini-review |
title_sort |
subcellular clearance and accumulation of huntington disease protein: a mini-review |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2016-04-01 |
description |
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 ubiquitin-proteasome system 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 of examining mHtt clearance and accumulation in different subcellular regions |
topic |
Autophagy Aggregation Huntingtin neurodegeneration Proteasome |
url |
http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00027/full |
work_keys_str_mv |
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1716796220416983040 |