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β Subunits of Voltage-gated Sodium Channels Are Novel Substrates of β-Site Amyloid Precursor Protein-cleaving Enzyme (BACE1) and γ-Secretase
Open accessAbstract
Sequential processing of amyloid precursor protein (APP) by membrane-bound proteases, BACE1 and gamma-secretase, plays a crucial role in the pathogenesis of Alzheimer disease. Much has been discovered on the properties of these proteases; however, regulatory mechanisms of enzyme-substrate interaction in neurons and their involvement in pathological changes are still not fully understood. It is mainly because of the membrane-associated cleavage of these proteases and the lack of information on new substrates processed in a similar way to APP. Here, using RNA interference-mediated BACE1 knockdown, mouse embryonic fibroblasts that are deficient in either BACE1 or presenilins, and BACE1-deficient mouse brain, we show clear evidence that beta subunits of voltage-gated sodium channels are sequentially processed by BACE1 and gamma-secretase. These results may provide new insights into the underlying pathology of Alzheimer disease.
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Metadata
- Authors
- Wong, H.-K., Sakurai, T., Oyama, F., Kaneko, K., Wada, K., Miyazaki, H., Kurosawa, M., De Strooper, B., Saftig, P., & Nukina, N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 280
- Issue
- 24
- Pages
- 23009-23017
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2003659505
- Cited by
- 290
- References
- 6
- FWCI
- 11.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
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