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Neuron survival kit

The insulin growth factor 1/Akt pathway is neuroprotective in Huntington's disease and is mediated by direct phosphorylation of huntingtin.

Tudor Toma(t.toma@ic.ac.uk)

Huntington's disease (HD) is caused by a mutation in the protein huntingtin. Patients with HD classically show involuntary muscular movements, personality changes and ultimately dementia, but the molecular mechanism involved in the development of the disorder has been poorly understood. In June Developmental Cell, Sandrine Humbert and colleagues from Institut Curie, Centre Universitaire, Orsay, France, show that the insulin growth factor 1/Akt pathway is neuroprotective in HD and is mediated by direct phosphorylation of huntingtin (Dev Cell 2002, 2:831-837).

Humbert et al. used primary cultures of striatal neurons and observed that IGF-1 and Akt inhibit mutant huntingtin-induced cell death. In addition they observed that huntingtin is a substrate of Akt and that phosphorylation of huntingtin by Akt is crucial to mediate the neuroprotective effects of IGF-1. They also found that Akt is altered in HD patients, which would support a role for IGF-1/Akt in HD....

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