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MINI REVIEW article

Front. Mol. Biosci.
Sec. Protein Biochemistry for Basic and Applied Sciences
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1527313

The N17 domain of huntingtin as a multifaceted player in Huntington's disease

Provisionally accepted
Hyunju Cho Hyunju Cho *
  • Institute for Basic Science (IBS), Daejeon, Republic of Korea

The final, formatted version of the article will be published soon.

    Huntington's disease (HD) is primarily caused by the aberrant aggregation of the N-terminal exon 1 fragment of mutant huntingtin protein (mHttex1) with expanded polyglutamine (polyQ) repeats in neurons. The first 17 amino acids of the N-terminus of Httex1 (N17 domain) immediately preceding the polyQ repeat domain are evolutionarily conserved across vertebrates and play multifaceted roles in the pathogenesis of HD. Due to its amphipathic helical properties, the N17 domain and the membrane-associated N17 domain promote mHttex1 aggregation. Diverse post-translational modifications (PTMs) in the N17 domain alter the aggregation state, thus modulating the cellular toxicity of mHttex1. Furthermore, the N17 domain serves as a nuclear export signal (NES) and mediates cytoplasmic localization of mHttex1. This review summarizes the four main roles of the N17 domain in regulating HD pathology and discusses potential therapeutic approaches targeting this N17 domain to relieve HD progression.

    Keywords: Huntington's disease1, Huntingtin2, N17 domain3, aggregation4, post-translational modification (PMT)5

    Received: 13 Nov 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hyunju Cho, Institute for Basic Science (IBS), Daejeon, Republic of Korea

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