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

Trinucleotide repeat expansion in neurological disease

A R La Spada1, H L Paulson, K H Fischbeck

  • 1Department of Laboratory Medicine, University of Washington Medical Center, Seattle 98195.

Annals of Neurology
|December 1, 1994
PubMed
Summary

Trinucleotide repeat expansion causes many neurological diseases, including fragile X syndrome and Huntington's disease. Expanding CAG repeats in genes leads to polyglutamine tract expansion, a common mechanism in inherited neurodegenerative disorders.

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

Intercellular transmission of pathogenic proteins in ALS: Exploring the pathogenic wave.

Neurobiology of disease·2023
Same author

[Progressive myoclonic epilepsy in the department of neurology of the University Teaching hospital Point "G"].

Le Mali medical·2023
Same author

Chronic BMAA exposure combined with TDP-43 mutation elicits motor neuron dysfunction phenotypes in mice.

Neurobiology of aging·2023
Same author

Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo.

Gene therapy·2016
Same author

Spinal and bulbar muscular atrophy: pathogenesis and clinical management.

Oral diseases·2013
Same author

The ubiquitin ligase F-box/G-domain protein 1 promotes the degradation of the disease-linked protein torsinA through the ubiquitin-proteasome pathway and macroautophagy.

Neuroscience·2012

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • Trinucleotide repeat expansion is a significant cause of inherited neurological disorders.
  • Seven diseases, including fragile X syndromes, myotonic dystrophy, Huntington's disease, and spinocerebellar ataxia, are linked to repeat expansions.
  • These expansions are unstable, leading to anticipation, where disease severity increases across generations.

Purpose of the Study:

  • To compare the clinical and molecular characteristics of trinucleotide repeat expansion diseases.
  • To classify these disorders based on repeat location and expansion size.
  • To explore the role of polyglutamine tract expansion in neurodegeneration.

Main Methods:

  • Review of existing literature on trinucleotide repeat expansion disorders.

Related Experiment Videos

  • Classification of diseases based on genetic and clinical features.
  • Comparison of molecular mechanisms underlying different repeat expansion diseases.

    • Main Results:

    • Trinucleotide repeat diseases can be categorized into two types based on repeat location: untranslated regions (fragile X, myotonic dystrophy) and protein-coding regions (SBMA, Huntington's disease, SCA1, DRPLA).
    • Disorders caused by expansions in protein-coding regions involve CAG repeats, which encode polyglutamine tracts.
    • Polyglutamine tract expansion is identified as a common pathogenic mechanism in these neurodegenerative diseases.

    Conclusions:

    • Polyglutamine tract expansion is a unifying mechanism for several inherited neurodegenerative disorders.
    • While a toxic gain-of-function effect is presumed for expanded polyglutamine tracts, the precise basis of neuronal toxicity is yet to be elucidated.
    • Further research is needed to understand the molecular basis of neuronal toxicity in CAG trinucleotide repeat disorders.