What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy

In the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia...

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Main Authors: Charlotte Kilstrup-Nielsen, Laura Rusconi, Paolo La Montanara, Dalila Ciceri, Anna Bergo, Francesco Bedogni, Nicoletta Landsberger
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2012/728267
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author Charlotte Kilstrup-Nielsen
Laura Rusconi
Paolo La Montanara
Dalila Ciceri
Anna Bergo
Francesco Bedogni
Nicoletta Landsberger
author_facet Charlotte Kilstrup-Nielsen
Laura Rusconi
Paolo La Montanara
Dalila Ciceri
Anna Bergo
Francesco Bedogni
Nicoletta Landsberger
author_sort Charlotte Kilstrup-Nielsen
collection DOAJ
description In the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia, and often the presence of some Rett-syndrome-like features. The association of CDKL5 with neurodevelopmental disorders and its high expression levels in the maturing brain underscore the importance of this kinase for proper brain development. However, our present knowledge of CDKL5 functions is still rather limited. The picture that emerges from the molecular and cellular studies suggests that CDKL5 functions are important for regulating both neuronal morphology through cytoplasmic signaling pathways and activity-dependent gene expression in the nuclear compartment. This paper surveys the current state of CDKL5 research with emphasis on the clinical symptoms associated with mutations in CDKL5, the different mechanisms regulating its functions, and the connected molecular pathways. Finally, based on the available data we speculate that CDKL5 might play a role in neuronal plasticity and we adduce and discuss some possible arguments supporting this hypothesis.
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institution OA Journals
issn 2090-5904
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language English
publishDate 2012-01-01
publisher Wiley
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series Neural Plasticity
spelling doaj-art-53a5c07b60b2436aa84c4e742f6a68622025-08-20T02:05:31ZengWileyNeural Plasticity2090-59041687-54432012-01-01201210.1155/2012/728267728267What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic EncephalopathyCharlotte Kilstrup-Nielsen0Laura Rusconi1Paolo La Montanara2Dalila Ciceri3Anna Bergo4Francesco Bedogni5Nicoletta Landsberger6Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, ItalyTheoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, ItalyTheoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, ItalyTheoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, ItalyTheoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, ItalySan Raffaele Rett Research Center, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, ItalyTheoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, ItalyIn the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia, and often the presence of some Rett-syndrome-like features. The association of CDKL5 with neurodevelopmental disorders and its high expression levels in the maturing brain underscore the importance of this kinase for proper brain development. However, our present knowledge of CDKL5 functions is still rather limited. The picture that emerges from the molecular and cellular studies suggests that CDKL5 functions are important for regulating both neuronal morphology through cytoplasmic signaling pathways and activity-dependent gene expression in the nuclear compartment. This paper surveys the current state of CDKL5 research with emphasis on the clinical symptoms associated with mutations in CDKL5, the different mechanisms regulating its functions, and the connected molecular pathways. Finally, based on the available data we speculate that CDKL5 might play a role in neuronal plasticity and we adduce and discuss some possible arguments supporting this hypothesis.http://dx.doi.org/10.1155/2012/728267
spellingShingle Charlotte Kilstrup-Nielsen
Laura Rusconi
Paolo La Montanara
Dalila Ciceri
Anna Bergo
Francesco Bedogni
Nicoletta Landsberger
What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy
Neural Plasticity
title What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy
title_full What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy
title_fullStr What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy
title_full_unstemmed What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy
title_short What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy
title_sort what we know and would like to know about cdkl5 and its involvement in epileptic encephalopathy
url http://dx.doi.org/10.1155/2012/728267
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