Sez6 and Sez6L were selected due to their predominant cleavage by BACE1, and their potential role in synaptic function that may contribute to presentation of seizures and/or motor impairments in NPC patients.
Beta-secretase 1 (BACE1) is attracting increasing attention for its vital role in pathogenesis of many neuropsychiatric disorders and many studies also have indicated BACE1 as a possible risk factor for seizures, but not any studies have reported association between BACE1 gene polymorphisms and seizures.
Of the BACE1 substrates that have been validated to date, a number may contribute to the synaptic deficits seen with BACE blockade, including neuregulin 1, close homologue of L1 and seizure-related gene 6.