January 16, 2007

Neuroscience

Too Much Of A Good Thing May Cause Huntington's

Mutant huntingtin protein increases neuronal calcium and stimulates excess neurotransmission

Sophie Rovner

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 help to explain the link between the protein and the disease.

Working with mutant fruit flies, the researchers found that accumulation of the abnormal huntingtin 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 (Neuron 2008, 57, 27).

Genetically reducing neuronal calcium content to normal levels in the flies prevents the increase in neurotransmission and the resulting neurodegeneration. These findings 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 the disease. Examples include compounds that would modulate neurotransmission or that would block the membrane pores through which calcium enters neurons.

Chemical & Engineering News

ISSN 0009-2347

Copyright © 2008 American Chemical Society