In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 30, No. 11 ( 2010-03-17), p. 3973-3982
Abstract:
Developmental and pathological death of neurons requires activation of a defined pathway of cell cycle proteins. However, it is unclear how this pathway is regulated and whether it is relevant in vivo . A screen for transcripts robustly induced in cultured neurons by DNA damage identified Sertad1, a Cdk4 (cyclin-dependent kinase 4) activator. Sertad1 is also induced in neurons by nerve growth factor (NGF) deprivation and Aβ (β-amyloid). RNA interference-mediated downregulation of Sertad1 protects neurons in all three death models. Studies of NGF withdrawal indicate that Sertad1 is required to initiate the apoptotic cell cycle pathway since its knockdown blocks subsequent pathway events. Finally, we find that Sertad1 expression is required for developmental neuronal death in the cerebral cortex. Sertad1 thus appears to be essential for neuron death in trophic support deprivation in vitro and in vivo and in models of DNA damage and Alzheimer's disease. It may therefore be a suitable target for therapeutic intervention.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.6421-09.2010
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2010
detail.hit.zdb_id:
1475274-8
SSG:
12
Bookmarklink