Huntington, or Huntington's, disease is a progressive neurodegenerative genetic disorder, which typically becomes noticeable at middle age, and is characterized by problems with muscle coordination, combined with cognitive decline and dementia, according to a January 2007 article published in "Lancet." The genetic mutation that causes Huntington's disease can be passed on from either parent, with a 50 percent chance of inheritance if one parent is affected.
Genetics
All people have two copies of the HTT gene, which can carry a mutation that causes Huntington's disease. The mutant HTT gene encodes a protein known as mHtt that's presence is associated with damage to particular areas of the brain, although the mechanism is not well understood, according to an article published in "Molecular Cell" in September 2004.
mHtt
Multiple theories have been proposed to explain the adverse effects of the mHtt protein on the brain, according to an article published in August 2003 in "Expert Reviews in Molecular Medicine." As cells produce MHtt, fragments of the mutant protein break off and deposit in cells causing toxic effects, leading to death of certain brain cells that have an abundance of the mHtt protein. Interaction of the MHtt protein with other cellular proteins such as Rhes is also thought to cause toxic effects associated with the death of brain cells, according to an article published in "Science" in June 2009.
HTT Gene
The HTT gene is located on the short arm of chromosome four, and contains a three letter sequence of DNA bases, CAG, which is repeated multiple times in Huntingdon's patients. People with Huntingdon disease usually have over 40 CAG repeats in the HTT gene, and a greater number than this is associated with an earlier onset of symptoms, according to Huntington's Disease Lighthouse.
Basal Ganglia
Damage to a brain region called the basal ganglia is characteristic of Huntington's, and is known to occur in the early stages of the disease. The basal ganglia is particularly involved in movement and behavior control, and also become damaged in other movement disorders such as Parkinson's disease, according to an article published in January 2007 in "Lancet."
Other Brain Areas
Damage to layers two, three and six of the cerebral cortex is common in people with Huntington's disease, and the severity correlates with increases in cognitive impairment and dementia, according to an article published in "Lancet" in January 2007. The cerebral cortex is involved in a myriad of activities including memory, perceptual awareness, attention, thought, language, and consciousness, and damage to this region of the brain is particularly associated with decreased cognitive abilities, according to The British National Health Service.
References
- PubMed; "Lancet"; Huntington's Disease; F. Walker; Jan 2007
- The HD Lighthouse: Your Proactive Fight Against HD
- PubMed; "Expert Reviews in Molecular Medicine"; Huntington's Disease: Molecular Basis of Neurodegeneration; August 2003
- PubMed; "Science"; Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity; June 2009
- PubMed; "Molecular Cell"; A Protein Interaction Network Links GIT1, an Enhancer of Huntingtin Aggregation, to Huntington's disease; H. Goehler; September 2004
