Molecular Strategies to Target Protein Aggregation in Huntington’s Disease

Huntington’s disease (HD) is a neurodegenerative disorder caused by the aggregation of the mutant huntingtin (mHTT) protein in nerve cells. mHTT self-aggregates to form soluble oligomers and insoluble fibrils, which interfere in a number of key cellular functions. This leads to cell quiescence and u...

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Autores principales:	Olga D. Jarosińska, Stefan G. D. Rüdiger
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	proteostasis huntingtin (HTT) protein fibrils aggregation protein quality control protein degradation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/66295db1c0e842b6b8f7b2b621ab8a97
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spelling	oai:doaj.org-article:66295db1c0e842b6b8f7b2b621ab8a972021-11-12T06:35:18ZMolecular Strategies to Target Protein Aggregation in Huntington’s Disease2296-889X10.3389/fmolb.2021.769184https://doaj.org/article/66295db1c0e842b6b8f7b2b621ab8a972021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.769184/fullhttps://doaj.org/toc/2296-889XHuntington’s disease (HD) is a neurodegenerative disorder caused by the aggregation of the mutant huntingtin (mHTT) protein in nerve cells. mHTT self-aggregates to form soluble oligomers and insoluble fibrils, which interfere in a number of key cellular functions. This leads to cell quiescence and ultimately cell death. There are currently still no treatments available for HD, but approaches targeting the HTT levels offer systematic, mechanism-driven routes towards curing HD and other neurodegenerative diseases. This review summarizes the current state of knowledge of the mRNA targeting approaches such as antisense oligonucleotides and RNAi system; and the novel methods targeting mHTT and aggregates for degradation via the ubiquitin proteasome or the autophagy-lysosomal systems. These methods include the proteolysis-targeting chimera, Trim-Away, autophagosome-tethering compound, autophagy-targeting chimera, lysosome-targeting chimera and approach targeting mHTT for chaperone-mediated autophagy. These molecular strategies provide a knowledge-based approach to target HD and other neurodegenerative diseases at the origin.Olga D. JarosińskaOlga D. JarosińskaStefan G. D. RüdigerStefan G. D. RüdigerFrontiers Media S.A.articleproteostasishuntingtin (HTT)protein fibrilsaggregationprotein quality controlprotein degradationBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	proteostasis huntingtin (HTT) protein fibrils aggregation protein quality control protein degradation Biology (General) QH301-705.5
spellingShingle	proteostasis huntingtin (HTT) protein fibrils aggregation protein quality control protein degradation Biology (General) QH301-705.5 Olga D. Jarosińska Olga D. Jarosińska Stefan G. D. Rüdiger Stefan G. D. Rüdiger Molecular Strategies to Target Protein Aggregation in Huntington’s Disease
description	Huntington’s disease (HD) is a neurodegenerative disorder caused by the aggregation of the mutant huntingtin (mHTT) protein in nerve cells. mHTT self-aggregates to form soluble oligomers and insoluble fibrils, which interfere in a number of key cellular functions. This leads to cell quiescence and ultimately cell death. There are currently still no treatments available for HD, but approaches targeting the HTT levels offer systematic, mechanism-driven routes towards curing HD and other neurodegenerative diseases. This review summarizes the current state of knowledge of the mRNA targeting approaches such as antisense oligonucleotides and RNAi system; and the novel methods targeting mHTT and aggregates for degradation via the ubiquitin proteasome or the autophagy-lysosomal systems. These methods include the proteolysis-targeting chimera, Trim-Away, autophagosome-tethering compound, autophagy-targeting chimera, lysosome-targeting chimera and approach targeting mHTT for chaperone-mediated autophagy. These molecular strategies provide a knowledge-based approach to target HD and other neurodegenerative diseases at the origin.
format	article
author	Olga D. Jarosińska Olga D. Jarosińska Stefan G. D. Rüdiger Stefan G. D. Rüdiger
author_facet	Olga D. Jarosińska Olga D. Jarosińska Stefan G. D. Rüdiger Stefan G. D. Rüdiger
author_sort	Olga D. Jarosińska
title	Molecular Strategies to Target Protein Aggregation in Huntington’s Disease
title_short	Molecular Strategies to Target Protein Aggregation in Huntington’s Disease
title_full	Molecular Strategies to Target Protein Aggregation in Huntington’s Disease
title_fullStr	Molecular Strategies to Target Protein Aggregation in Huntington’s Disease
title_full_unstemmed	Molecular Strategies to Target Protein Aggregation in Huntington’s Disease
title_sort	molecular strategies to target protein aggregation in huntington’s disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/66295db1c0e842b6b8f7b2b621ab8a97
work_keys_str_mv	AT olgadjarosinska molecularstrategiestotargetproteinaggregationinhuntingtonsdisease AT olgadjarosinska molecularstrategiestotargetproteinaggregationinhuntingtonsdisease AT stefangdrudiger molecularstrategiestotargetproteinaggregationinhuntingtonsdisease AT stefangdrudiger molecularstrategiestotargetproteinaggregationinhuntingtonsdisease
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Molecular Strategies to Target Protein Aggregation in Huntington’s Disease

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