Once the polyQ region exceeds 36 repeats, it becomes unstable and the protein produced has different properties. Non-Huntington’s sufferers have 36 or fewer repeats of CAG in their Htt gene, resulting in the production of normal cytoplasmic Htt (Strachan & Read, 2011). This paper showed where the mutation occurred, providing an insight into how the disease manifested in patients. A major breakthrough came in 1993 when the gene responsible was located at 4p16.3 (Huntington's Disease Collaborative Research Project, 1993). In 1911, further research by Charles Davenport confirmed the genetic link and showed it was an autosomal dominant disorder (Davenport, 1911). He noticed that there was a high prevalence of the then unexplained condition amongst certain families- up to this point, sufferers had been thought to be possessed due to the chorea.

The condition was first described by George Huntington (Huntington, 1872). This new protein is pathogenic and causes neurodegeneration, leading to cognitive decline and progressive chorea. This large polyglutamine (polyQ) expanse results in the production of mutant Huntingtin (muHtt), in a gain of function dynamic mutation (Landles & Bates, 2004). It is an expansion disorder, caused by an increase in the number of CAG (glutamine) repeats in the coding region of the gene for Huntingtin (Htt) protein on chromosome 4p16.3. Huntington’s disease (HD) is an autosomal dominant repeat disorder with complete penetrance and prevalence of around 4-8 per 100,000 (Harper, 1992). This review will critically assess research that has been conducted into Huntington’s disease and propose possible future work. Much research has been directed towards finding treatments for the condition and while some show progress, the scientific community is still some way away from a definitive therapy to slow or prevent the disease. Mutant Huntingtin has been extensively studied and its effects on cells noted but questions regarding its toxicity remain to be answered. It is known that Huntingtin is ubiquitously expressed and has interactions with many different cellular components. However, the exact mechanism of pathogenesis, or even the exact role of the normal Huntingtin protein are not comprehensively understood. It is caused by an increase in a polyglutamine region of the Huntingtin protein, resulting in a toxic gain of function mutation. Huntington’s disease is a progressive neurodegenerative disorder that affects around five people in every 100,000. 6.5 Replacement of Lost Neurons- Stem Cell Therapy.6.4 Aggregation Prevention- The Role of Molecular Chaperones.6.3 Reduction in Pathogenic Protein Levels- Down regulation of the Mutant Gene.6.2 Current Disease Management Strategies.6.1 The TRACK-HD Study and the Hurdles With Monitoring Disease Progression.4.3 Impairment of the Ubiquitin-Proteasome System.4.2 Metabolic Dysfunction in Huntington’s Disease.4.1 Huntingtin Aggregates and Inclusion Bodies.muHtt And Its Role In The Pathology of Huntington’s Disease 3.3 The Roles of Wild Type Huntingtin Protein- Transcription.3.2 The Roles of Wild Type Huntingtin Protein- Cellular Transport.3.1 The Roles of Wild Type Huntingtin Protein- Development.2.4 Familial Inheritance and Anticipation.2.2 Juvenile Onset Huntington’s Disease.

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