Huntington's disease is a neurodegenerative disorder
affecting many (possibly all) parts of the brain. Onset usually occurs between thirty and fifty years of age, and the symptoms become progressively worse over the next ten or fifteen. Death is often due to pneumonia
, as the Huntington's victim eventually becomes unable to cough well enough to clear the lungs of infectious matter
. The primary symptom, uncontrollable movements known as chorea
, comes from the death of neurons in the basal ganglia
. Other symptoms include loss of general intellectual function as well as dementia, both caused by neuron death in other brain areas, notably over the entire cerebral cortex.
Mutation of a single gene, named huntingtin, seems to be entirely responsible for the disease. A repeated sequence of CAG codons is part of the huntingtin protein's structure, even when it is working correctly. When a stuttering mutation causes there to be 36 or more repeats, the huntingtin protein will be pathological, and the victim will eventually get Huntington's. With 35 or fewer repeats, no symptoms or problems will ever occur. Because of this easily identified genetic basis, testing can be done to determine positively whether or not a patient will get Huntington's later in life.
Exactly how the mutant huntingtin protein interferes with neurons is still in question, with new research being published monthly. One theory is that the long chain of glutamine (which is coded for by CAG) can become entangled with the glutamine chains of other proteins, such as CPB. These entanglements would aggregate and cause plaques that are dangerous to the neuron, much as with Alzheimer's disease. Another possibility is that the mutant huntingtin protein interferes with brain-derived neurotrophic factor (BDNF). This is supported by the fact that neurons with the BDNF gene knocked out die in much the same way as Huntington's neurons, and that cells cultured with the mutant huntingtin produce little or no BDNF.
The precise mechanism of neuron death in Huntington's is also not known, but some general features are. Neuron death appears to be caused by excitotoxicity, much like the Olney's lesions caused by interference with NMDA channels. Excitotoxicity happens when a neuron is flooded excitatory amino acids (glutamate in particular) released from surrounding neurons. Neuron death follows from excitotoxicity because the neuron is overstimulated for too long a period, which overheats it to the point of death -- the neuron literally burns out. When each neuron dies it releases stored up excitatory amino acids, and the process continues in a chain reaction. This process is probably made much worse by the damage already done to neurons by the huntingtin proteins, as described above.
Both the mechanism and area non-selectivity of this process closely resemble the damage done in Olney's lesions. I would guess that the brain damage done by extreme dissociative drug abuse would closely resemble early stages of Huntington's disease.