Mitogen-Activated Protein Kinase Phosphatase (MKP)-1 as a Neuroprotective Agent: Promotion of the Morphological Development of Midbrain Dopaminergic Neurons
In: NeuroMolecular Medicine, Jg. 15 (2013-04-13), S. 435-446
Online
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Zugriff:
A greater understanding of the mechanisms that promote the survival and growth of dopaminergic neurons is essential for the advancement of cell replacement therapies for Parkinson's disease (PD). Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Here, we show that MKP-1 is expressed in dopaminergic neurons cultured from E14 rat ventral mesencephalon (VM). When dopaminergic neurons were transfected to overexpress MKP-1, they displayed a more complex morphology than their control counterparts in vitro. Specifically, MKP-1-transfection induced significant increases in neurite length and branching with a maximum increase observed in primary branches. We demonstrate that inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in vitro is mediated by p38 and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. We further show that overexpression of MKP-1 in dopaminergic neurons contributes to neuroprotection against the effects of 6-OHDA. Collectively, we report that MKP-1 can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Thus, we propose that strategies aimed at augmenting MKP-1 expression or activity may be beneficial in protecting dopaminergic neurons and may provide potential therapeutic approaches for PD.
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Mitogen-Activated Protein Kinase Phosphatase (MKP)-1 as a Neuroprotective Agent: Promotion of the Morphological Development of Midbrain Dopaminergic Neurons
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Autor/in / Beteiligte Person: | Toulouse, André ; Sullivan, Aideen M. ; Nolan, Yvonne M. ; Wyatt, Sean ; Collins, Louise M. ; Long-Smith, Caitriona M. ; O'Keeffe, Gerard W. |
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Zeitschrift: | NeuroMolecular Medicine, Jg. 15 (2013-04-13), S. 435-446 |
Veröffentlichung: | Springer Science and Business Media LLC, 2013 |
Medientyp: | unknown |
ISSN: | 1559-1174 (print) ; 1535-1084 (print) |
DOI: | 10.1007/s12017-013-8230-5 |
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