Jove
Visualize
Contact Us
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 Videos

Pathogenic superoxide dismutase structure, folding, aggregation and turnover.

P John Hart1

  • 1Department of Biochemistry, Department of Veterans Affairs, South Texas Veterans Health Care System, The University of Texas Health Science Center at San Antonio, 78229-3900, USA. pjhart@biochem.uthscsa.edu

Current Opinion in Chemical Biology
|March 7, 2006
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Activation of human RNA lariat debranching enzyme Dbr1 by binding protein TTDN1 occurs though an intrinsically disordered C-terminal domain.

The Journal of biological chemistry·2023
Same author

Crystal Structure of the RNA Lariat Debranching Enzyme Dbr1 with Hydrolyzed Phosphorothioate RNA Product.

Biochemistry·2022
Same author

A pH Switch Controls Zinc Binding in Tomato Copper-Zinc Superoxide Dismutase.

Biochemistry·2021
Same author

Why does oxamniquine kill Schistosoma mansoni and not S. haematobium and S. japonicum?

International journal for parasitology. Drugs and drug resistance·2020
Same author

Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment.

PLoS pathogens·2019
Same author

Experimental Mutations in Superoxide Dismutase 1 Provide Insight into Potential Mechanisms Involved in Aberrant Aggregation in Familial Amyotrophic Lateral Sclerosis.

G3 (Bethesda, Md.)·2019
Same journal

Function through shape: An overview of DNA G-quadruplexes in transcriptional regulation.

Current opinion in chemical biology·2026
Same journal

Advances in tools and technologies for multiplexed bioluminescence imaging.

Current opinion in chemical biology·2026
Same journal

High-resolution molecular mapping by expansion-coupled label-free and multimodal imaging.

Current opinion in chemical biology·2026
Same journal

Recent advances in glycoconjugate-based therapeutics.

Current opinion in chemical biology·2026
Same journal

Towards better red emitters for bioimaging: Innovations in rhodamine and cyanine chemistry.

Current opinion in chemical biology·2026
Same journal

Chemigenetic fluorescent biosensors in biological imaging - New trends and advances.

Current opinion in chemical biology·2026
See all related articles

Mutant copper-zinc superoxide dismutase (SOD1) proteins destabilize and aggregate, leading to inherited amyotrophic lateral sclerosis (ALS). Motor neuron protein turnover systems may be overwhelmed, with breakdown products potentially driving disease progression.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease.
  • Mutations in human cytosolic copper-zinc superoxide dismutase (SOD1) cause inherited ALS.
  • Understanding the molecular basis of SOD1-linked ALS is crucial for developing therapies.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which SOD1 mutations lead to inherited ALS.
  • To investigate the structural destabilization and aggregation pathways of mutant SOD1.
  • To explore the role of protein turnover and breakdown products in ALS pathogenesis.

Main Methods:

  • Biophysical studies to assess protein structure and stability.
  • Analysis of metal ion and disulfide bond roles in SOD1 destabilization.

Related Experiment Videos

  • Investigation of SOD1 aggregation in mouse models of ALS.
  • Studies on motor neuron protein turnover and proteolytic products.

    • Main Results:

    • Pathogenic SOD1 mutations destabilize key structural elements (loops, beta-barrels).
    • Loss of metal ions and disulfide bond reduction exacerbate SOD1 destabilization.
    • Mutant SOD1 aggregation occurs late in disease models, suggesting overwhelmed cellular systems.
    • Proteolytic breakdown products of SOD1 may contribute to disease pathogenesis.

    Conclusions:

    • SOD1 destabilization and aggregation are central to inherited ALS.
    • Motor neuron protein quality control mechanisms are compromised in SOD1-ALS.
    • Further research into SOD1 turnover and breakdown products is warranted for therapeutic strategies.