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Huntington's disease: seeing the pathogenic process through a genetic lens
James F Gusella1, Marcy E MacDonald
1Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA. gusella@helix.mgh.harvard.edu
Trends in Biochemical Sciences
|July 11, 2006
Summary
Huntington's disease is caused by an expanded CAG repeat in the huntingtin gene. Focusing on early disease stages and intact huntingtin protein may lead to effective treatments for this neurodegenerative disorder.
Area of Science:
- Neurodegenerative Disorders
- Genetics
- Molecular Biology
Background:
- Huntington's disease (HD) is caused by an expanded CAG trinucleotide repeat, leading to an elongated polyglutamine tract in the huntingtin protein.
- Previous research focused on N-terminal huntingtin fragments, but genetic evidence suggests intact huntingtin is key.
Purpose of the Study:
- To re-evaluate the role of intact huntingtin in Huntington's disease pathogenesis.
- To identify new therapeutic targets by focusing on the earliest stages of the disease.
Main Methods:
- Review of genetic and biochemical strategies in Huntington's disease research.
- Analysis of the impact of expanded polyglutamine in intact huntingtin.
Main Results:
- Genetic strategies indicate that expanded polyglutamine in intact huntingtin triggers the disease process.
- Focusing on early, presymptomatic stages is crucial for understanding pathogenesis.
Conclusions:
- Understanding the role of intact huntingtin and early disease stages is essential for developing effective Huntington's disease treatments.
- Incorporating genetic insights from patients can guide the search for biochemical targets to prevent or slow disease onset.