PubMed Journals: Dev Cell
Source: PMID: 12062094
⇦ ⇨ Dev Cell. 2002 Jun;2(6):831-7.
The IGF-1/Akt pathway is neuroprotective
in Huntington's disease and involves Huntingtin
phosphorylation by Akt.
Humbert S(1), Bryson EA, Cordelières FP,
Connors NC, Datta SR, Finkbeiner S, Greenberg
ME, Saudou F.
(1) UMR 146 CNRS/Institut Curie, Centre Universitaire,
91405 Orsay Cedex, France.
In the search for neuroprotective factors
in Huntington's disease, we found that insulin
growth factor 1 via activation of the
serine/threonine kinase Akt/PKB is able
to inhibit neuronal death specifically induced
by mutant huntingtin containing an expanded
polyglutamine stretch. The IGF-1/Akt pathway
has a dual effect on huntingtin-induced
toxicity, since activation of this pathway
also results in a decrease in the formation
of intranuclear inclusions of mutant huntingtin.
We demonstrate that huntingtin is a substrate
of Akt and that phosphorylation of huntingtin
by Akt is crucial to mediate the neuroprotective
effects of IGF-1. Finally, we show that
Akt is altered in Huntington's disease patients.
Taken together, these results support a
potential role of the Akt pathway in Huntington's
PMID: 12062094 [Indexed for MEDLINE]