A5074036885- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Genomic variations and chromosomal abnormalities
- Ubiquitin and proteasome pathways
- 14-3-3 protein interactions
- Neurogenesis and neuroplasticity mechanisms
The Francis Crick Institute
2023-2024
Abstract CDKL5 is a brain-enriched serine/threonine kinase, associated with profound developmental and epileptic encephalopathy called deficiency disorder (CDD). To design targeted therapies for CDD, it essential to determine where expressed active in the brain test if compensatory mechanisms exist at cellular level. We generated conditional Cdkl5 knockout mice excitatory neurons, inhibitory neurons astrocytes. assess activity, we utilized phosphospecific antibody phosphorylated EB2,...
Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (
Despite mediating several essential processes in the brain, including during development, cyclin-dependent kinase-like 5 (CDKL5) remains a poorly characterized human protein kinase. Accordingly, its substrates, functions, and regulatory mechanisms have not been fully described. We realized that availability of potent selective small molecule probe targeting CDKL5 could enable illumination roles normal development as well diseases where it has become aberrant due to mutation. prepared analogs...
Despite mediating several essential processes in the brain, including during development, cyclin-dependent kinase-like 5 (CDKL5) remains a poorly characterized human protein kinase. Accordingly, its substrates, functions, and regulatory mechanisms have not been fully described. We realized that availability of potent selective small molecule probe targeting CDKL5 could enable illumination roles normal development as well diseases where it has become aberrant due to mutation. prepared analogs...
Abstract Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 ( CDKL5 ) cause deficiency disorder (CDD), a rare and severe neurodevelopmental associated with medically refractory early-life epilepsy, motor, cognitive, visual autonomic disturbances the absence of any structural brain pathology. Analysis genetic variants CDD have indicated that kinase function is central to disease encodes serine-threonine significant homology GSK3β, which has also been linked synaptic...