Developmental cell, 2002-06, Vol.2 (6), p.831-837
2002
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- Autor(en) / Beteiligte
- Titel
- The IGF-1/Akt Pathway Is Neuroprotective in Huntington's Disease and Involves Huntingtin Phosphorylation by Akt
- Ist Teil von
- Developmental cell, 2002-06, Vol.2 (6), p.831-837
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2002
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1534-5807eISSN: 1878-1551DOI: 10.1016/S1534-5807(02)00188-0Titel-ID: cdi_proquest_miscellaneous_18429949
- Format
- –
- Schlagworte
- Cell Death, Cells, Cultured, Corpus Striatum - cytology, Enzyme Activation, Humans, Huntingtin Protein, Huntington Disease - genetics, Huntington Disease - pathology, Inclusion Bodies - metabolism, Insulin-Like Growth Factor I - metabolism, Nerve Tissue Proteins - chemistry, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Neurons - cytology, Neurons - metabolism, Nuclear Proteins - chemistry, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Phosphorylation, Point Mutation, Protein-Serine-Threonine Kinases - metabolism, Proto-Oncogene Proteins - metabolism, Proto-Oncogene Proteins c-akt, Recombinant Fusion Proteins - metabolism, Substrate Specificity