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, 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.
Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy.
Charlotte
C
Kilstrup-Nielsen
Laura
L
Rusconi
Paolo
P
La Montanara
Dalila
D
Ciceri
Anna
A
Bergo
Francesco
F
Bedogni
Nicoletta
N
Landsberger
D000818:Animals; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D065768:Lennox Gastaut Syndrome; D009154:Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism
D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human