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