How Huntingtin Protein Kills Neurons

French researchers have discovered how the deadly changes that lead to Huntington's disease are caused.

French researchers from the Institut Curie, Orsay—who published their study results in the August 12 issue of Neuron—have discovered how the deadly changes that lead to Huntington’s disease are caused by a defective huntingtin protein. Specifically, they have revealed that the protein likely disrupts neurogenesis and thus decreases neural progenitor cells.

The study is the first to decipher the role played by the huntingtin protein in neuronal development, which is likely related to the deadly effects of Huntington’s disease, despite knowledge that it is implicated in numerous cellular functions, like signaling, transport, binding, and apoptosis.

"For a while it has been known that huntingtin was involved in vesicle transport; they took it a step further to ask what else might be impacted by it," Scott Zeitlin, neuroscientist, University of Virginia School of Medicine, told The Scientist.

When Humbert’s team silenced huntingtin in dividing cells, the cells couldn’t accurately orient their spindles and thus progenitor cells became misaligned and produced more neurons, not more neuronal progenitor cells. Without these progenitor cells, neurons are unable to be produced in the brain when older neurons dies.

"Some people have, for a while, hypothesized that there could be a developmental aspect for Huntington's disease, this at least gives you a window of where to look to see where it may be occurring," said Zeitlin. "Most people think of this disease as a late-onset disorder, but there are always things that could be laid down early in development that could predispose these neurons to problems later."

Learn more about the study findings here, or check out the article in Neuron.

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