ParkinsonCanadaV1, Main, Exploration, bibRecord, 001994

SERTAD1 PLAYS AN ESSENTIAL ROLE IN DEVELOPMENTAL AND PATHOLOGICAL NEURON DEATH

Identifieur interne : 001994 ( Main/Exploration ); précédent : 001993; suivant : 001995

SERTAD1 PLAYS AN ESSENTIAL ROLE IN DEVELOPMENTAL AND PATHOLOGICAL NEURON DEATH

Auteurs : Subhas C. Biswas [États-Unis] ; Yi Zhang [Canada] ; Grace Iyirhiaro [Canada] ; Ryan T. Willett [États-Unis] ; Yasmilde Rodriguez Gonzalez [Canada] ; Sean P. Cregan ; Ruth S. Slack [Canada] ; David S. Park [Canada] ; Lloyd A. Greene [États-Unis]

Source :

The Journal of neuroscience : the official journal of the Society for Neuroscience [ 0270-6474 ] ; 2010.

RBID : PMC:2861041

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 cyclin dependent kinase 4 (Cdk4) activator. Sertad1 is also induced in neurons by nerve growth factor (NGF) deprivation and β-amyloid (Aβ). RNAi-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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861041

DOI: 10.1523/JNEUROSCI.6421-09.2010
PubMed: 20237268
PubMed Central: 2861041

Affiliations:

Canada, États-Unis

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p id="P1">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 <italic>in vivo</italic>
. A screen for transcripts robustly induced in cultured neurons by DNA damage identified Sertad1, a cyclin dependent kinase 4 (Cdk4) activator. Sertad1 is also induced in neurons by nerve growth factor (NGF) deprivation and β-amyloid (Aβ). RNAi-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 <italic>in vitro</italic>
 and <italic>in vivo</italic>
 and in models of DNA damage and Alzheimer’s disease. It may therefore be a suitable target for therapeutic intervention.</p>
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La maladie de Parkinson au Canada (serveur d'exploration)

SERTAD1 PLAYS AN ESSENTIAL ROLE IN DEVELOPMENTAL AND PATHOLOGICAL NEURON DEATH

SERTAD1 PLAYS AN ESSENTIAL ROLE IN DEVELOPMENTAL AND PATHOLOGICAL NEURON DEATH

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Abstract

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	La maladie de Parkinson au Canada (serveur d'exploration)
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