Molecular and Synaptic Bases of CDKL5 Disorder
The X‐linked gene cyclin‐dependent kinase‐like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early‐onset epileptic encephalopathy and severe intellectual disability, suggesting...
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| Published in | Developmental neurobiology (Hoboken, N.J.) Vol. 79; no. 1; pp. 8 - 19 |
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| Main Authors | , |
| Format | Journal Article |
| Language | English |
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United States
Wiley Subscription Services, Inc
01.01.2019
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| Abstract | The X‐linked gene cyclin‐dependent kinase‐like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early‐onset epileptic encephalopathy and severe intellectual disability, suggesting that CDKL5 plays important roles in brain development and function. Recent studies using cultured neurons, knockout mice, and human iPSC‐derived neurons have demonstrated that CDKL5 regulates axon outgrowth, dendritic morphogenesis, and synapse formation. The role of CDKL5 in maintaining synaptic function in the mature brain has also begun to emerge. Moreover, mouse models that are deficient for CDKL5 recapitulate some of the key clinical phenotypes in human patients. Here we review these findings related to the function of CDKL5 in the brain and discuss the underlying molecular and cellular mechanisms. |
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| AbstractList | The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early-onset epileptic encephalopathy and severe intellectual disability, suggesting that CDKL5 plays important roles in brain development and function. Recent studies using cultured neurons, knockout mice, and human iPSC-derived neurons have demonstrated that CDKL5 regulates axon outgrowth, dendritic morphogenesis, and synapse formation. The role of CDKL5 in maintaining synaptic function in the mature brain has also begun to emerge. Moreover, mouse models that are deficient for CDKL5 recapitulate some of the key clinical phenotypes in human patients. Here we review these findings related to the function of CDKL5 in the brain and discuss the underlying molecular and cellular mechanisms. The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early-onset epileptic encephalopathy and severe intellectual disability, suggesting that CDKL5 plays important roles in brain development and function. Recent studies using cultured neurons, knockout mice, and human iPSC-derived neurons have demonstrated that CDKL5 regulates axon outgrowth, dendritic morphogenesis, and synapse formation. The role of CDKL5 in maintaining synaptic function in the mature brain has also begun to emerge. Moreover, mouse models that are deficient for CDKL5 recapitulate some of the key clinical phenotypes in human patients. Here we review these findings related to the function of CDKL5 in the brain and discuss the underlying molecular and cellular mechanisms.The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early-onset epileptic encephalopathy and severe intellectual disability, suggesting that CDKL5 plays important roles in brain development and function. Recent studies using cultured neurons, knockout mice, and human iPSC-derived neurons have demonstrated that CDKL5 regulates axon outgrowth, dendritic morphogenesis, and synapse formation. The role of CDKL5 in maintaining synaptic function in the mature brain has also begun to emerge. Moreover, mouse models that are deficient for CDKL5 recapitulate some of the key clinical phenotypes in human patients. Here we review these findings related to the function of CDKL5 in the brain and discuss the underlying molecular and cellular mechanisms. The X‐linked gene cyclin‐dependent kinase‐like 5 ( CDKL5 ) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early‐onset epileptic encephalopathy and severe intellectual disability, suggesting that CDKL5 plays important roles in brain development and function. Recent studies using cultured neurons, knockout mice, and human iPSC‐derived neurons have demonstrated that CDKL5 regulates axon outgrowth, dendritic morphogenesis, and synapse formation. The role of CDKL5 in maintaining synaptic function in the mature brain has also begun to emerge. Moreover, mouse models that are deficient for CDKL5 recapitulate some of the key clinical phenotypes in human patients. Here we review these findings related to the function of CDKL5 in the brain and discuss the underlying molecular and cellular mechanisms. |
| Author | Xiong, Zhi‐Qi Zhu, Yong‐Chuan |
| Author_xml | – sequence: 1 givenname: Yong‐Chuan orcidid: 0000-0003-4979-0149 surname: Zhu fullname: Zhu, Yong‐Chuan organization: Chinese Academy of Sciences – sequence: 2 givenname: Zhi‐Qi surname: Xiong fullname: Xiong, Zhi‐Qi email: xiongzhiqi@ion.ac.cn organization: Chinese Academy of Sciences |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30246934$$D View this record in MEDLINE/PubMed |
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| Snippet | The X‐linked gene cyclin‐dependent kinase‐like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been... The X‐linked gene cyclin‐dependent kinase‐like 5 ( CDKL5 ) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been... The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been... |
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| SubjectTerms | Animal models Animals CDKL5 dendritic spine Encephalopathy Epilepsy Epileptic Syndromes - genetics Epileptic Syndromes - pathology Humans intellectual disability kinase Morphogenesis Neurodevelopmental disorders Phenotypes Protein-Serine-Threonine Kinases - genetics Protein-serine/threonine kinase Rett syndrome Rodents Spasms, Infantile - genetics Spasms, Infantile - pathology Synapses Synapses - pathology Synaptogenesis |
| Title | Molecular and Synaptic Bases of CDKL5 Disorder |
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