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Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
Department of Neurology, University of Göttingen, Robert-Koch Str. 40 37075 Göttingen, Germany
DFG-Research Center for Molecular Physiology of the Brain (CMPB), Humboldtallee 23, 37075 Göttingen, Germany
Department 828, Molecular Neurobiology, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark
* Author to whom correspondence should be addressed.
Received: 11 February 2010; in revised form: 16 April 2010 / Accepted: 21 April 2010 / Published: 23 April 2010
Abstract: Cdk5 is essential for neuronal differentiation processes in the brain. Activation of Cdk5 requires the association with the mostly neuron-specific p35 or p39. Overactivation of CDK5 by cleavage of p35 into p25 is thought to be involved in neurodegenerative processes. Here, we have tested an approach to inhibit pathological Cdk5 activation with a Tat-linked dominant-negative fragment of p25. It reduced cell death induced by staurosporine and showed a tendency to alleviate manganese-induced cell death, while it did not protect against 6-OHDA toxicity. Our results suggest that the Tat technique is a suitable tool to inhibit dysregulated CDK5.
Keywords: Cdk5; Tat-technique; neurodegenerative diseases
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Liman, J.; Weishaupt, J.H.; Bähr, M.; Dietz, G.P. Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration. Pharmaceuticals 2010, 3, 1232-1240.
Liman J, Weishaupt JH, Bähr M, Dietz GP. Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration. Pharmaceuticals. 2010; 3(4):1232-1240.
Liman, Jan; Weishaupt, Jochen H.; Bähr, Mathias; Dietz, Gunnar P.H. 2010. "Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration." Pharmaceuticals 3, no. 4: 1232-1240.