The X-linked Cyclin-dependent kinase-like 5 (CDKL5) gene encodes a protein kinase the functions of which are required for normal brain functions. Indeed, mutations in CDKL5 cause severe neurological disorders characterized by the onset of seizures in the first few months of life, intellectual disabilities, motor dysfunctions, sleep disturbances etc. The neuronal defects underlying these clinical manifestations are not fully understood.
The research of our laboratory is focused on identifying the molecular network belonging to CDKL5 in order to understand the basis for the neuronal dysfunctions linked to loss of CDKL5 and to identify novel drug-based therapeutic strategies for CDKL5-related disorders.
Through our past research we have contributed significantly to the current knowledge on CDKL5 functions by:
- showing that CDKL5 and the Rett syndrome causing gene MECP2 belong to common molecular pathways;
- describing the functional consequences of some disease causing mutations in CDKL5;
- describing the expression pattern of CDKL5 in the developing brain;
- showing that CDKL5 regulates axon specification and outgrowth through its interaction with shootin1;
- showing that CDKL5 expression is tightly controlled upon neuronal activation through a complex mechanism involving its local translation and proteasomal degradation depending on specific changes in its phosphorylation pattern.
