• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase.

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 ID: 15824102

Authors

  • Wong HK
  • Sakurai T
  • Oyama F
  • Kaneko K
  • Wada K
  • Miyazaki H
  • Kurosawa M
  • De Strooper B
  • Saftig P
  • Nukina N

Journal

The Journal of biological chemistry

Publication Data

June 17, 2005

Associated Grants

None

Mesh Terms

  • Alzheimer Disease
  • Amino Acid Sequence
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor
  • Animals
  • Aspartic Acid Endopeptidases
  • Binding Sites
  • Blotting, Western
  • Brain
  • Cell Line
  • Cell Membrane
  • Cells, Cultured
  • Detergents
  • Endopeptidases
  • Fibroblasts
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Neurons
  • Phosphoric Monoester Hydrolases
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Interference
  • Sequence Homology, Amino Acid
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transfection