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Updated: Jan 18, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

10.0K

Membranes as targets and modifiers of mutant huntingtin aggregation

Justin Legleiter1

  • 1Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA.

Trends in Biochemical Sciences
|September 10, 2025
PubMed

Insights

Huntington's disease involves mutant huntingtin protein aggregation on cellular membranes. Understanding these interactions may reveal new therapeutic targets for this neurodegenerative disorder.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder.
  • It is caused by an expanded CAG repeat in the huntingtin (HTT) gene.
  • This leads to an expanded polyglutamine (polyQ) tract in the HTT protein, forming mutant HTT (mHTT) that aggregates.

Purpose of the Study:

  • To review membrane abnormalities in various HD models.
  • To explore the interplay between mHTT binding to membranes and subsequent aggregation.
  • To emphasize the role of N-terminal mHTT fragments in these interactions.

Main Methods:

  • Review of existing literature on Huntington's disease models.
  • Analysis of studies focusing on mHTT-membrane interactions.
  • Examination of mHTT aggregation dynamics on cellular membranes.

Main Results:

  • Membrane abnormalities are observed across different HD models.
  • Cellular membranes influence mHTT aggregation in complex ways.
  • mHTT interacts with and accumulates on cellular membranes, particularly N-terminal fragments.

Conclusions:

  • Membrane interactions are a significant factor in HD pathogenesis.
  • Understanding mHTT-lipid interactions could offer novel therapeutic strategies.
  • Targeting these membrane interactions may complement existing therapeutic approaches for HD.

Keywords:
Huntington’s diseaseamyloidlipidsneurodegenerationpolyglutamine

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