Einfluss des ß-site-APP-cleaving enzyme 1 (BACE1) auf den spannungsabhängigen Natriumkanal Nav1.2

Schmidt-Neuenfeldt, Karoline

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.

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Schmidt-Neuenfeldt, Karoline: Einfluss des ß-site-APP-cleaving enzyme 1 (BACE1) auf den spannungsabhängigen Natriumkanal Nav1.2. 2009.

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