000K utf8 1100 $c2010 1500 ger 2050 urn:nbn:de:gbv:8-diss-42040 3000 Schmidt-Neuenfeldt, Karoline 4000 Einfluss des ß-site-APP-cleaving enzyme 1 (BACE1) auf den spannungsabhängigen Natriumkanal Nav1.2$hChristian-Albrechts-Universität zu Kiel [Schmidt-Neuenfeldt, Karoline] 4000 Non-proteolytic effect of ß-site APP-cleaving enzyme (BACE1) on sodium channel function$hChristian-Albrechts-Universität zu Kiel [Schmidt-Neuenfeldt, Karoline] 4030 Kiel$nChristian-Albrechts-Universität zu Kiel 4209 The ß-site APP-cleaving enzyme 1 (BACE1) is widely known for its pivotal role in the amyloidogenic pathway leading to Alzheimer`s disease. Here, we elaborate on the recent finding that auxiliary subunits of voltage-gated sodium channels (ß2 and ß4) are BACE substrates. BACE1 produced complex effects on sodium channel gating that could be only partially explained by ß2/ß4 cleavage. To characterize the unexpected non-proteolytic effect of BACE1, we examined HEK cells co-transfected with only Nav1.2 and either normal or catalytically inactive BACE1. Both BACE1 variants produced virtually identical effects on sodium channel gating, which would lead to enhanced cellular exitability. The non-proteolytic BACE1 effect on Nav1.2 current was confirmed in murine neuroblastoma cells, which express sodium channels endogenously, but lack ß2 and ß4. Our study reveals an important facet og BACE1 function that should help to decipher he role of BACE1 in normal and demented brain. 4950 https://nbn-resolving.org/urn:nbn:de:gbv:8-diss-42040$xR$3Volltext$534 4961 https://macau.uni-kiel.de/receive/diss_mods_00004204 5051 610 5550 BACE1 5550 BACE1 5550 Nav1.2 5550 Nav1.2