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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Main Authors: Ting eZhao, Yan eHong, Xiao-Jiang eLi, Shihua eLi
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-04-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00027/full
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spelling 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
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AT yanehong subcellularclearanceandaccumulationofhuntingtondiseaseproteinaminireview
AT xiaojiangeli subcellularclearanceandaccumulationofhuntingtondiseaseproteinaminireview
AT shihuaeli subcellularclearanceandaccumulationofhuntingtondiseaseproteinaminireview
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