Huntington's Disease

Huntington’s Disease is a neurodegenerative disorder that follows an autosomal dominant pattern of inheritance with complete penetrance. It is caused by a mutation that encodes an increase in CAG repeats, which encodes glutamine, in the N-terminus of the gene encoding Huntingtin (HTT) on chromosome 4. Normal individuals, typically have 9 to 36 CAG repeats, therefore Huntington’s disease is characterized by more than 36 CAG repeats.  (Trottier 1995)

Figure 1: Distribution of the number of CAG repeats within a population. Indicates the split within a population, in which individual with normal HTT have a low number of repeats and individual with a high number of repeats have mHTT (Huntington’s disease) Figure from

Onset of Huntington’s disease typically occurs later in life, around 30 to 40 years of age (though cases of juvenile Huntington’s disease exist). Phenotypically Huntington’s disease is characterized by motor dysfunction, cognitive disorders, personality changes, weight loss, and chorea appearing during typical age of onset. Mutant Huntingtin (mHTT) is a misfolded and toxic protein that alters the transcription and epigenetic regulation of dozens of proteins. (Valor 2014)

Figure 1: Summary of inheritance, mechanism of disease state, and symptoms of Huntington’s Disease

Treatment of Huntington’s is very limited and pharmacological drugs used in the treatment and management of Huntington’s predominantly only provide relief from the symptoms; drugs that help control movement disorders. However more potential drug candidates and drug targets are being found and understood faster than  ever before. Research using HD models of Huntington’s Disease have provided potential new mechanism for treating Huntington’s disease, such as inhibition of histone deacetylase (HDAC). HDAC is activity is increased by mHTT, which subsequently leads to the inactivation of other genes. Introduction of an HDAC inhibitor can lower HDAC activity back to normal rates. However, to reduce the potential of an overdose from HDAC inhibition, increasing the levels of β-hydroxybutyrate (β-OHB), and endogenous HDAC inhibitor, via a ketogenic diet has been shown to improve the condition of Huntington’s disease and other neurodegenerative disorders. (Valor 2015)

Other pages:

History and Metabolic Context

Molecular Basis of the Disease State

Treatment and Management of Disease

Conclusions and Future Work

Annotated Bibliography



Trottier, Y., D. Devys, G. Imbert, F. Saudou, I. An, Y. Lutz, C. Weber, Y. Agid, E. C. Hirsch, and J. L. Mandel. 1995. “Cellular Localization of the Huntington’s Disease Protein and Discrimination of the Normal and Mutated Form.” Nature Genetics 10 (1): 104–10. doi:10.1038/ng0595-104

Valor, Luis M. 2015. “Epigenetic-Based Therapies in the Preclinical and Clinical Treatment of Huntington’s Disease.” International Journal of Biochemistry & Cell Biology 67 (October): 45–48. doi:10.1016/j.biocel.2015.04.009.

Valor, Luis M., and Deisy Guiretti. 2014. “What’s Wrong with Epigenetics in Huntington’s Disease?” Neuropharmacology, Neuroepigenetic Disorders, 80 (May): 103–14. doi:10.1016/j.neuropharm.2013.10.025.

9 Replies to “Huntington's Disease”

  1. This was really interesting! I didn’t know much about Huntingson’s Disease at all besides that I recognized the name so I found this very informative. I liked how it explained when it happens to people and what it does to a person who has it.

  2. I found your article on Huntington’s disease very insightful and educational. I especially liked how you described the mutation in greater depth, telling what sequence repeats and what amino acid is constructed. I think that one thing you could further elaborate on is the function of HDAC.

    1. Thanks for commenting! I will elaborate on the function of HDAC, and its role in Huntington’s disease in one of the pages of Huntington’s Disease. I will also try to make HDAC’s role more clear in this title page.

  3. I found the description of the genetic aspects of the disease a bit challenging to follow as a non-scientist. The graphics were instructive and the references would be useful for follow-up to learn more about the disease. I would have liked to read more about treatment of Huntington’s Disease.

    1. Thank you for the comment. I tried to include most of the genetic terms in the the biochemistry primer page, but I will also try to breakdown the genetics aspects a bit more for a better explanation. For further information on the treatment of Huntington’s Disease, there will be a separate page devoted to discussing treatment option.

  4. Very informative page however I just wish you would have defined what CAG repeats actually are because I was confused reading this coming from a non-science background.

    1. Thanks for the comment! I will try to make the definition of the CAG repeats more clear on this page. The CAG repeats is a region of the protein, Huntingtin. The region is a string of multiple glutamines, an amino acid. A string of too many amino acids produces the mutant form of huntingtin and results in Huntington’s disease.

  5. I liked the overall explanation of Huntington’s, but at the onset of the title page there is no specific explanation of ‘CAG repeats’ and this was a weak link with which to begin. I could never put into context what the normal 9-36 CAG repeats meant so it felt a bit uneasy continuing with the rest even though it was very well explained and supported. Also, just as a piece of interesting information, the composer of ‘This Land is Your Land’, Woody Guthrie, died of Huntington’s. Good job!

    1. Thanks for the comment! I will try to make that more clear in the title page. The CAG repeats is a region of the protein, huntingtin, that consists of a string of the amino acid, glutamine. The 9-36 CAG repeats signifies the number of glutamines in that region and results in the normal protein, which does not result in Huntington’s Disease. Greater than 36 CAG repeats results in the mutant protein and produces Huntington’s Disease. I hope this made things more clear.

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