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Review
. 2017 Jul 5;7(7):a024240.
doi: 10.1101/cshperspect.a024240.

Huntington's Disease: Mechanisms of Pathogenesis and Therapeutic Strategies

Maria Jimenez-Sanchez  1 , Floriana Licitra  1 , Benjamin R Underwood  2 , David C Rubinsztein  1
Affiliations
Review

Huntington's Disease: Mechanisms of Pathogenesis and Therapeutic Strategies

Maria Jimenez-Sanchez et al. Cold Spring Harb Perspect Med. .

Abstract

Huntington's disease is a late-onset neurodegenerative disease caused by a CAG trinucleotide repeat in the gene encoding the huntingtin protein. Despite its well-defined genetic origin, the molecular and cellular mechanisms underlying the disease are unclear and complex. Here, we review some of the currently known functions of the wild-type huntingtin protein and discuss the deleterious effects that arise from the expansion of the CAG repeats, which are translated into an abnormally long polyglutamine tract. Finally, we outline some of the therapeutic strategies that are currently being pursued to slow down the disease.

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Figures

Figure 1.
Figure 1.
Schematic of selected mechanisms of pathogenesis in Huntington’s disease (HD). BDNF, Brain-derived neurotrophic factor; ROS, reactive oxygen species; NMDAR, N-methyl-D-aspartate receptor.
See this image and copyright information in PMC

References

    1. Ali NJ, Levine MS. 2006. Changes in expression of N-methyl-D-aspartate receptor subunits occur early in the R6/2 mouse model of Huntington’s disease. Dev Neurosci 28: 230–238. - PubMed
    1. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F, Lin B, Kalchman MA. 1993. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington’s disease. Nat Genet 4: 398–403. - PubMed
    1. Arenas J, Campos Y, Ribacoba R, Martín MA, Rubio JC, Ablanedo P, Cabello A. 1998. Complex I defect in muscle from patients with Huntington’s disease. Ann Neurol 43: 397–400. - PubMed
    1. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. 2004. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431: 805–810. - PubMed
    1. Aziz NA, van der Burg JMM, Landwehrmeyer GB, Brundin P, Stijnen T, EHDI Study Group, Roos RAC. 2008. Weight loss in Huntington disease increases with higher CAG repeat number. Neurology 71: 1506–1513. - PubMed

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