Related Experiment Videos
Abnormal expression of cdk5 in focal cortical dysplasia in humans
Sanjay M Sisodiya1, Maria Thom, Woan Ru Lin
1Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. sisodiya@ion.ucl.ac.uk
Abstract:
Focal cortical dysplasia (FCD) is an important cause of refractory epilepsy in humans. The origin of its pathognomonic abnormal cell types and the links between abnormal cell morphology and epileptogenicity remain unknown. The developmentally-regulated kinase cdk5 and its neuronal activator p35 are known to be central to a number of key components in neuronal development, cellular morphology, cytoskeletal function, synaptic plasticity and neurodegeneration. Here we examine eight cases of human FCD for expression of cdk5. We show abnormal cdk5 immunoreactivity and aggregation of protein suggesting alterations in cdk5 may also be involved in this important epileptogenic human pathology.
Insights
Alterations in the cdk5 protein, crucial for neuronal development, were observed in human focal cortical dysplasia (FCD). This suggests a potential role for cdk5 in the pathology of this epilepsy-causing brain malformation.
Area of Science:
- Neuroscience
- Cell Biology
- Epilepsy Research
Background:
- Focal cortical dysplasia (FCD) is a significant cause of drug-resistant epilepsy.
- The cellular origins and mechanisms linking abnormal cell structure to seizures in FCD are not fully understood.
Purpose of the Study:
- To investigate the expression and localization of cyclin-dependent kinase 5 (cdk5) in human FCD tissues.
- To explore the potential involvement of cdk5 alterations in the epileptogenesis associated with FCD.
Main Methods:
- Analysis of eight human FCD cases.
- Immunohistochemical examination for cdk5 expression and aggregation.
Main Results:
- Abnormal cdk5 immunoreactivity was detected in FCD samples.
- Evidence of protein aggregation suggests dysregulation of cdk5 in FCD.
Conclusions:
- Altered cdk5 expression and potentially aberrant protein aggregation are implicated in human FCD.
- These findings suggest cdk5 pathway dysregulation may contribute to the epileptogenicity of FCD.