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The Role of Polyglutamine Expansions in Huntington’s Disease

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‘Huntington’s disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by personality changes, motor impairment and subcortical dementia. It is associated with a selective neuronal cell death occurring primarily in the cortex and striatum.’ (Scherzinger et al, 1997). HD causes emotional problems, uncontrolled movements and the loss of thinking ability. It can lead to disability and death from the illness. There are two forms of this disease: adult-onset and early-onset (juvenile).

Adult onset is by the far most common for HD; symptoms develop at mid 30s/40s, an individual will live an average of 20 years after symptoms and signs begin. Premature signs and symptoms are depression, involuntary movements, trouble learning new information, poor coordination and balance; this can all progress very severely. When HD develops into twitching or jerking this is referred as Chorea. HD can be referred to Huntington Chorea. ‘HD usually has a mid-life onset, but a juvenile form, defined by onset of symptoms before the age of 21 years, is present in about 7% of HD cases.’ (Nance, 2001) It has similar symptoms however the disease progresses more quickly than adult onset form. Gente (1985) results showed findings by others, that the most juvenile-onset patients inherit the gene from their fathers and that the late-onset form is more frequently inherited from affected mothers.

‘The disorder is caused by CAG/polyglutamine (poly Q) repeat expansions in the first exon of a gene encoding a large ~350 kDa protein of unknown function.’ (Scherzinger et al, 1997) Zhang et al state that due to the expansion of polyQ repeats within the protein

causes neurodegenerative disease. Expansion of CAG repeats coding f...

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..., C. and Bates, G, P. (2004). Huntingtin and the molecular pathogenesis of Huntington’s disease. EMBO reports 5. 958-963

Nance, M, A. and Myers, R, H. (2001)

Panov, A, V., Gutekunst, C., Leavitt, B, R., Hayden, M, R., Burke, J, R., Strittmatter, W, J. And Greenamyre, J, T. (2002) Early mitochondrial calcium defects in Huntington’s Disease are a direct effect of Polyglutamines. Nature neuroscience. Volume 5 no 8

Ross, C, A. (2002). Polyglutamine Pathogenesis: Emergence of Unifying Mechanism for Huntington’s Disease and Related Disorders. Neuron, Vol. 35,819-822.

Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, Birgit., Hasenbank, R., Bates, G, P., Davies, S, W., Lehrach, H and Wanker, E, E. (1997). Huntington-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo. Cell, Vol.90, 549-558.

Zhang,
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