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Urocortin modulates dopaminergic neuronal survival via inhibition of glycogen synthase kinase-3β and histone deacetylase

Urocortin modulates dopaminergic neuronal survival via inhibition of glycogen synthase kinase-3β and histone deacetylase,10.1016/j.neurobiolaging.2009

Urocortin modulates dopaminergic neuronal survival via inhibition of glycogen synthase kinase-3β and histone deacetylase   (Citations: 2)
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Urocortin (UCN) is a member of the corticotropin-releasing hormone (CRH) family of neuropeptides that regulates stress responses. Although UCN is principally expressed in dopaminergic neurons in rat substantia nigra (SN), the function of UCN in modulating dopaminergic neuronal survival remains unclear. Using primary mesencephalic cultures, we demonstrated that dopaminergic neurons underwent spontaneous cell death when their age increased in culture. Treatment of mesencephalic cultures with UCN markedly prolonged the survival of dopaminergic neurons, whereas neutralization of UCN with anti-UCN antibody accelerated dopaminergic neurons degeneration. UCN increased intracellular cAMP levels followed by phosphorylating glycogen synthase kinase-3β (GSK-3β) on Ser9. Moreover, UCN directly inhibited the histone deacetylase (HDAC) activity and induced a robust increase in histone H3 acetylation levels. Using pharmacological approaches, we further demonstrated that inhibition of GSK-3β and HDAC contributes to UCN-mediated neuroprotection. These results suggest that dopaminergic neurons-derived UCN might be involved in an autocrine protective signaling mechanism.
Journal: Neurobiology of Aging - NEUROBIOL AGING , vol. 32, no. 9, pp. 1662-1677, 2011
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    • ...Urocortin also protects from spontaneous cell death related to aging (Huang et al., 2009)...
    • ...Urocortin mediates its effects through at least two high affinity membrane receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRF2R), which are expressed not only in SNc dopaminergic neurons but also in various neurons and glial cells (Huang et al., 2009; Kim et al., 2009; Pedersen et al., 2002; Stevens et al., 2003)...
    • ...Urocortin increases intracellular cAMP levels followed by phospholyation of GSK3β that contributes to urocortin-mediated protection in spontaneous cell death related to aging (Huang et al., 2009)...

    Yonjung Kimet al. Protective effect of urocortin on 1-methyl-4-phenylpyridinium-induced ...

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