MICAL-1 oxidoreductase activity induces disassembly of actin filaments, thereby regulating the organization of the actin cytoskeleton in developing and adult neurons and in other cell types. This suggests that dysregulation of the actin cytoskeleton dynamics is a likely mechanism by which MICAL-1 pathogenic variants lead to ADLTE. Ann Neurol 2018;83:483-493.
Autosomal dominant lateral temporal epilepsy (ADTLE) is an inherited epileptic syndrome characterized by ictal auditory symptoms or aphasia, negative MRI findings, and relatively benign evolution. Mutations responsible for ADLTE have been found in the LGI1 gene. The functions of the Lgi1 protein apparently are mediated by interactions with members of the ADAM protein family: it binds the postsynaptic receptor ADAM22 to regulate glutamate-AMPA currents at excitatory synapses and also the ADAM23 receptor to promote neurite outgrowth in vitro and dendritic arborization in vivo. Because alteration of each of these neuronal mechanisms may underlie ADLTE, ADAM22 and ADAM23 are candidate genes for this syndrome. In a previous work, we excluded a major role of ADAM22 in the aetiology of ADLTE. Here, we performed linkage analysis between microsatellite markers within or flanking the ADAM23 gene and ADLTE in 13 Italian families. The results exclude ADAM23 as major causative gene for ADLTE.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.