|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0002716,
umls-concept:C0014442,
umls-concept:C0037492,
umls-concept:C0205314,
umls-concept:C0330390,
umls-concept:C0379528,
umls-concept:C0679622,
umls-concept:C1412727,
umls-concept:C1709634,
umls-concept:C1710236,
umls-concept:C1711351
|
|
pubmed:issue |
24
|
|
pubmed:dateCreated |
2005-6-13
|
|
pubmed:abstractText |
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.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
17
|
|
pubmed:volume |
280
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
23009-17
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:15824102-Alzheimer Disease,
pubmed-meshheading:15824102-Amino Acid Sequence,
pubmed-meshheading:15824102-Amyloid Precursor Protein Secretases,
pubmed-meshheading:15824102-Amyloid beta-Protein Precursor,
pubmed-meshheading:15824102-Animals,
pubmed-meshheading:15824102-Aspartic Acid Endopeptidases,
pubmed-meshheading:15824102-Binding Sites,
pubmed-meshheading:15824102-Blotting, Western,
pubmed-meshheading:15824102-Brain,
pubmed-meshheading:15824102-Cell Line,
pubmed-meshheading:15824102-Cell Membrane,
pubmed-meshheading:15824102-Cells, Cultured,
pubmed-meshheading:15824102-Detergents,
pubmed-meshheading:15824102-Endopeptidases,
pubmed-meshheading:15824102-Fibroblasts,
pubmed-meshheading:15824102-Genetic Vectors,
pubmed-meshheading:15824102-Humans,
pubmed-meshheading:15824102-Mice,
pubmed-meshheading:15824102-Mice, Inbred C57BL,
pubmed-meshheading:15824102-Mice, Knockout,
pubmed-meshheading:15824102-Microscopy, Fluorescence,
pubmed-meshheading:15824102-Molecular Sequence Data,
pubmed-meshheading:15824102-Neurons,
pubmed-meshheading:15824102-Phosphoric Monoester Hydrolases,
pubmed-meshheading:15824102-Protein Binding,
pubmed-meshheading:15824102-Protein Structure, Tertiary,
pubmed-meshheading:15824102-RNA Interference,
pubmed-meshheading:15824102-Sequence Homology, Amino Acid,
pubmed-meshheading:15824102-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:15824102-Transfection
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase.
|
|
pubmed:affiliation |
Laboratories for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
