Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration

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...

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Detalles Bibliográficos
Autores principales: Liman, Jan, Weishaupt, Jochen H., Bähr, Mathias, Dietz, Gunnar P.H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034031/
https://www.ncbi.nlm.nih.gov/pubmed/27713298
http://dx.doi.org/10.3390/ph3041232
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author Liman, Jan
Weishaupt, Jochen H.
Bähr, Mathias
Dietz, Gunnar P.H.
author_facet Liman, Jan
Weishaupt, Jochen H.
Bähr, Mathias
Dietz, Gunnar P.H.
author_sort Liman, Jan
collection PubMed
description 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.
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spelling pubmed-40340312014-05-27 Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration Liman, Jan Weishaupt, Jochen H. Bähr, Mathias Dietz, Gunnar P.H. Pharmaceuticals (Basel) Article 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. MDPI 2010-04-23 /pmc/articles/PMC4034031/ /pubmed/27713298 http://dx.doi.org/10.3390/ph3041232 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Liman, Jan
Weishaupt, Jochen H.
Bähr, Mathias
Dietz, Gunnar P.H.
Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
title Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
title_full Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
title_fullStr Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
title_full_unstemmed Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
title_short Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
title_sort cell-penetrating fragments of the cdk5 regulatory subunit are protective in models of neurodegeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034031/
https://www.ncbi.nlm.nih.gov/pubmed/27713298
http://dx.doi.org/10.3390/ph3041232
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AT bahrmathias cellpenetratingfragmentsofthecdk5regulatorysubunitareprotectiveinmodelsofneurodegeneration
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