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Updated: Jul 19, 2026
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Selective neuronal degeneration in Huntington's disease
Catherine M Cowan1, Lynn A Raymond
1Department of Psychiatry, Division of Neuroscience, Brain Research Centre University of British Columbia, Vancouver, British Columbia V6T 1Z3.
Current Topics in Developmental Biology
|September 21, 2006
Summary
Huntington's disease (HD) involves CAG expansion in the huntingtin gene, leading to neurodegeneration. NMDA receptor excitotoxicity and mitochondrial dysfunction are key factors in selective neuronal vulnerability in HD patients.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by movement, cognitive, and mood abnormalities.
- It stems from a CAG expansion in the huntingtin gene, causing an expanded polyglutamine tract in the huntingtin protein.
- Selective neuronal loss, particularly in the dorsal striatum, is a hallmark of HD.
Purpose of the Study:
- To investigate the mechanisms underlying selective neurodegeneration in Huntington's disease.
- To explore the roles of huntingtin protein function and dysfunction in HD pathogenesis.
- To identify key cellular processes contributing to neuronal vulnerability in HD.
Main Methods:
- Postmortem brain analyses of HD patients.
- Utilizing HD transgenic and knock-in mouse models.
- Subcellular fractionation and immunolocalization studies.
- Investigating alterations in N-methyl-d-aspartate (NMDA) receptor activity and mitochondrial function.
Main Results:
- Huntingtin protein is implicated in organelle transport, protein trafficking, and energy metabolism.
- Polyglutamine-expanded huntingtin impairs axonal transport and mitochondrial function.
- Alterations in NMDA receptor activity and mitochondrial dysfunction are early effects contributing to neuronal vulnerability.
Conclusions:
- NMDA receptor-mediated excitotoxicity and mitochondrial dysfunction play significant roles in the selective neuronal vulnerability observed in Huntington's disease.
- Understanding these mechanisms is crucial for developing targeted therapies for HD.
- Further research into huntingtin protein's normal function and the impact of its expanded form is warranted.
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