Jove
Visualize
Contact Us

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

11.4K
Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
11.4K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same journal

Design Principles for Negative Thermal Expansion in Two-Dimensional Materials.

Accounts of chemical research·2026
Same journal

Main Group Redox Catalysis: New Frontiers with Germanium and Tin.

Accounts of chemical research·2026
Same journal

Taming Irreversibility in sp<sup>2</sup>-Carbon-Conjugated COFs from Polycrystalline Powders to Single Crystals and Thin Films.

Accounts of chemical research·2026
Same journal

Electroactive Imidazolium Ionic Liquids in Organic Synthesis.

Accounts of chemical research·2026
Same journal

Calix[4]resorcinarene-Based Porous Organic Cages: Synthesis and Applications.

Accounts of chemical research·2026
Same journal

Light-Driven Dual Rotary Molecular Motors and Beyond.

Accounts of chemical research·2026
See all related articles
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Video

Updated: Dec 7, 2025

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

9.9K

Exploding the Repeat Length Paradigm while Exploring Amyloid Toxicity in Huntington's Disease.

Ronald Wetzel1

  • 1Department of Structural Biology, University of Pittsburgh School of Medicine, Biomedical Sciences Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15260, United States.

Accounts of Chemical Research
|September 25, 2020
PubMed
Summary
This summary is machine-generated.

Huntington's disease (HD) toxicity is linked to aggregated huntingtin protein (htt) forms, not just polyglutamine (polyQ) length. Amyloid aggregates, not monomers, are the likely toxic species driving this neurodegenerative disease.

More Related Videos

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

2.9K
Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-&#946; and Tau Neuropathology
10:02

Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology

Published on: May 28, 2017

27.7K

Related Experiment Videos

Last Updated: Dec 7, 2025

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

9.9K
Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

2.9K
Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-&#946; and Tau Neuropathology
10:02

Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology

Published on: May 28, 2017

27.7K

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder caused by expanded polyglutamine (polyQ) tracts in the huntingtin protein (htt).
  • Identifying the specific toxic htt species has been challenging due to numerous self-associated states and overlapping formation kinetics.
  • Previous research focused on polyQ length as the primary driver of toxicity.

Purpose of the Study:

  • To investigate the role of htt aggregation states in Huntington's disease toxicity.
  • To determine if amyloid aggregates, rather than polyQ repeat length, are the primary toxic species.
  • To develop novel htt variants to dissect aggregation pathways and toxicity.

Main Methods:

  • Engineered pro-β-hairpin (βHP) and β-breaker polyQ and htt-exon1 (htt-ex1) variants with specific mutations.
  • Utilized fluorescence correlation spectroscopy (FCS) and a novel thioflavin-T (ThT) assay to characterize htt-ex1 assembly intermediates.
  • Expressed engineered htt variants in mammalian cells (PC12), rat neuronal models, and *Drosophila* models of HD.

Main Results:

  • Expanded polyQ htt-ex1 versions showed tetramers, oligomers, and fibrils, but not monomers, correlating with early toxicity.
  • Engineered htt-ex1-βHP variants with short polyQ repeats but strong aggregation were toxic, challenging the repeat length paradigm.
  • Non-toxic β-breaker variants favored non-amyloid oligomers, while toxic βHP variants rapidly formed amyloid structures.

Conclusions:

  • Amyloid aggregates of huntingtin protein, rather than polyQ length or non-amyloid oligomers, are strongly implicated as the major toxic species in Huntington's disease.
  • The formation of the fundamental amyloid folding motif is critical for htt-induced toxicity.
  • Engineered htt variants provide powerful tools to study HD pathogenesis and break the traditional repeat length paradigm.