Stage-dependent involvement of ADAM10 and its significance in epileptic seizures

The prevalence of epileptic seizures in Alzheimer's disease (AD) has attracted an increasing amount of attention in recent years, and many cohort studies have found several risk factors associated with the genesis of seizures in AD. Among these factors, young age and severe dementia are seemingly contradictory and independent risk factors, indicating that the pathogenesis of epileptic seizures is, to a certain extent, stage-dependent. A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a crucial α-secretase responsible for ectodomain shedding of its substrates; thus, the function of this protein depends on the biological effects of its substrates. Intriguingly, transgenic models have demonstrated ADAM10 to be associated with epilepsy. Based on the biological effects of its substrates, the potential pathogenic roles of ADAM10 in epileptic seizures can be classified into amyloidogenic processes in the ageing stage and cortical dysplasia in the developmental stage. Therefore, ADAM10 is reviewed here as a stage-dependent modulator in the pathogenesis of epilepsy. Current data regarding ADAM10 in epileptic seizures were collected and reviewed for potential pathogenic roles (ie amyloidogenic processes and cortical dysplasia) and regulatory mechanisms (ie transcriptional and posttranscriptional regulation). These findings are then discussed in terms of the significance of the stage-dependent functions of ADAM10 in epilepsy. Several potential targets for seizure control, such as candidate transcription factors and microRNAs that regulate ADAM10, as well as potential genetic screening tools for the early recognition of cortical dysplasia, have been suggested but must be studied in more detail.