The emerging role of the first 17 amino acids of huntingtin in Huntington’s disease
Abstract: Huntington’s disease (HD) is caused by a polyglutamine (polyQ) domain that is expanded beyond a critical threshold near the N-terminus of the huntingtin (htt) protein, directly leading to htt aggregation. While full-length htt is a large (on the order of ∼350 kDa) protein, it is proteolyzed into a variety of N-terminal fragments that accumulate in oligomers, fibrils, and larger aggregates. It is clear that polyQ length is a key determinant of htt aggregation and toxicity. However, the flanking sequences around the polyQ domain, such as the first 17 amino acids on the N terminus (Nt17), influence aggregation, aggregate stability, influence other important biochemical properties of the protein and ultimately its role in pathogenesis. Here, we review the impact of Nt17 on htt aggregation mechanisms and kinetics, structural properties of Nt17 in both monomeric and aggregate forms, the potential role of posttranslational modifications (PTMs) that occur in Nt17 in HD, and the function of Nt17 as a membrane targeting domain.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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The emerging role of the first 17 amino acids of huntingtin in Huntington’s disease ; volume:6 ; number:1 ; year:2015 ; pages:33-46 ; extent:14
Biomolecular concepts ; 6, Heft 1 (2015), 33-46 (gesamt 14)
- Creator
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Arndt, James R.
Chaibva, Maxmore
Legleiter, Justin
- DOI
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10.1515/bmc-2015-0001
- URN
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urn:nbn:de:101:1-2409241634362.301295978040
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:36 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Arndt, James R.
- Chaibva, Maxmore
- Legleiter, Justin
Other Objects (12)
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Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models
Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington’s disease patients
Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
Disease-related Huntingtin seeding activities in cerebrospinal fluids of Huntington’s disease patients
Analysis of mutant huntingtin aggregation and toxicity in Drosophila models of Huntington’s disease
HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington’s disease mice
Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington’s disease
Making (anti-) sense out of huntingtin levels in Huntington disease
Siah-1-interacting protein regulates mutated huntingtin protein aggregation in Huntington’s disease models
Mutant huntingtin confers cell-autonomous phenotypes on Huntington’s disease iPSC-derived microglia
Salivary levels of total huntingtin are elevated in Huntington’s disease patients
Soluble mutant huntingtin drives early human pathogenesis in Huntington’s disease
Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models
Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington’s disease patients
Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
Disease-related Huntingtin seeding activities in cerebrospinal fluids of Huntington’s disease patients
Analysis of mutant huntingtin aggregation and toxicity in Drosophila models of Huntington’s disease
HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington’s disease mice
Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington’s disease
Making (anti-) sense out of huntingtin levels in Huntington disease
Siah-1-interacting protein regulates mutated huntingtin protein aggregation in Huntington’s disease models
Mutant huntingtin confers cell-autonomous phenotypes on Huntington’s disease iPSC-derived microglia
Salivary levels of total huntingtin are elevated in Huntington’s disease patients
Soluble mutant huntingtin drives early human pathogenesis in Huntington’s disease
Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models
Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington’s disease patients
Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
Disease-related Huntingtin seeding activities in cerebrospinal fluids of Huntington’s disease patients
Analysis of mutant huntingtin aggregation and toxicity in Drosophila models of Huntington’s disease
HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington’s disease mice
Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington’s disease
Making (anti-) sense out of huntingtin levels in Huntington disease
Siah-1-interacting protein regulates mutated huntingtin protein aggregation in Huntington’s disease models