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Updated: Jul 27, 2026
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Inclusions of R6/2 Mice Are Not Amyloid and Differ Structurally from Those of Huntington Disease Brain
William André1,2, Christophe Sandt2, Isabelle Nondier1
1Centre National de la Recherche Scientifique/Université Paris Descartes , UMR 8118, Laboratoire de Physiologie Cérébrale, 75006 Paris, France.
Analytical Chemistry
|April 12, 2017
Summary
Huntington disease inclusions in patients contain amyloid structures causing neuronal death, unlike those in R6/2 mice, which lack amyloid and neuronal loss. This structural difference explains varying disease pathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- R6/2 mice model Huntington disease (HD) with expanded polyQ huntingtin fragments.
- HD mouse models show inclusions but minimal neuronal death, unlike human HD patients.
Purpose of the Study:
- To investigate the structural differences in protein inclusions between R6/2 mice and human HD patients.
- To determine if amyloid structure correlates with neuronal toxicity in Huntington disease.
Main Methods:
- Synchrotron-based infrared microspectroscopy in transmission and attenuated total reflectance modes.
- Analysis of protein inclusions in the striatum and cortex of R6/2 mice and human HD patients.
Main Results:
- Inclusions in R6/2 mice showed no detectable amyloid structures.
- Proteins within R6/2 mouse inclusions were structurally indistinguishable from surrounding soluble proteins.
- Previously, human HD patient inclusions were found to be enriched in amyloid β-sheets.
Conclusions:
- The absence of amyloid structures in R6/2 mouse inclusions correlates with their lack of significant neuronal death.
- Amyloid structure in protein inclusions may be a key determinant of neuronal toxicity in Huntington disease.
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01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...