Huntington's Excess Neurotransmission

Huntington's disease is caused by an abnormal version of huntingtin protein. New findings reported by Baylor College of Medicine molecular biologist Juan Botas and colleagues now help explain the link between the protein and the disease (Neuron 2008, 57, 27). Working with mutant fruit flies, the researchers found that accumulation of the abnormal protein within presynaptic neurons increases levels of Ca²⁺ in the neurons. The extra calcium induces the presynaptic neurons to release excess neurotransmitters, which contributes to the development of the disease. Genetically reducing neuronal calcium content to normal levels in the flies prevents the increase in neurotransmission and the resulting neurodegeneration. These discoveries support the hypothesis that Ca²⁺ is involved in increased neurotransmission in the disease. The results also suggest that treatments could be developed to delay the onset and progression of Huntington's. Examples include compounds that would modulate neurotransmission or that would block the membrane pores through which Ca²⁺ enters neurons.