TBZ cannot fix the proteins that are damaged in HD, but it can help reduce one of their harmful effects: chorea. Recall that chorea is believed to be caused by increased activity of the neurotransmitter dopamine. TBZ exerts its anti-choreic effects by reducing the amount of dopamine in the brain in two ways. The first way and more widely recognized way is by preventing dopamine from being released into pockets at the end of each neuron called vesicles. These pockets store neurotransmitters, like dopamine, and release them into the synapse at certain times. When a signal to release the neurotransmitters is received, the vesicles are transported to the ends of nerve cells for release through the membraneof the neuron into the synapse. Special proteins called vesicular monoamine transporters (VMATs) are responsible for putting neurotransmitters into the vesicles. TBZ binds to the VMATs, preventing them from performing this function. As such, neurotransmitters like dopamine are not stored in vesicles and cannot be released into the synapse where they would otherwise affect other nerve cells.
The second way that TBZ reduces dopamine is by blocking dopamine receptors. TBZ binds to receptors on the surface of the receiving nerve cell, blocking dopamine from binding and passing on its message. The mechanism of inhibiting dopamine receptors, however, is thought to be less significant at the TBZ dosages used in HD patients. For more information on the neurobiology of HD, click here. Because it has the potential to block dopamine on both sides of the synapse, TBZ is thought to be that much more effective at treating choreic movement disorders.
Last Modified: 07/13/2009
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