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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Published in | Frontiers in molecular biosciences Vol. 8; p. 769184 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
12.11.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Edited by: Walid A Houry, University of Toronto, Canada Stefan Rüdiger ORCID Reviewed by: Swasti Raychaudhuri, Centre for Cellular and Molecular Biology (CCMB), India Axel Mogk, Heidelberg University, Germany Olga Jarosińska 0000-0002-2184-3993 This article was submitted to Protein Folding, Misfolding and Degradation, a section of the journal Frontiers in Molecular Biosciences 0000-0002-1807-2972 |
ISSN: | 2296-889X 2296-889X |
DOI: | 10.3389/fmolb.2021.769184 |