PMID- 10591213
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20101118
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 402
IP  - 6761
DP  - 1999 Dec 2
TI  - Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase
      activity.
PG  - 533-7
AB  - Mutations in the gene encoding the amyloid protein precursor (APP) cause
      autosomal dominant Alzheimer's disease. Cleavage of APP by unidentified
      proteases, referred to as beta- and gamma-secretases, generates the amyloid
      beta-peptide, the main component of the amyloid plaques found in Alzheimer's
      disease patients. The disease-causing mutations flank the protease cleavage sites
      in APP and facilitate its cleavage. Here we identify a new membrane-bound
      aspartyl protease (Asp2) with beta-secretase activity. The Asp2 gene is expressed
      widely in brain and other tissues. Decreasing the expression of Asp2 in cells
      reduces amyloid beta-peptide production and blocks the accumulation of the
      carboxy-terminal APP fragment that is created by beta-secretase cleavage.
      Solubilized Asp2 protein cleaves a synthetic APP peptide substrate at the
      beta-secretase site, and the rate of cleavage is increased tenfold by a mutation 
      associated with early-onset Alzheimer's disease in Sweden. Thus, Asp2 is a new
      protein target for drugs that are designed to block the production of amyloid
      beta-peptide peptide and the consequent formation of amyloid plaque in
      Alzheimer's disease.
FAU - Yan, R
AU  - Yan R
AD  - Cell & Molecular Biology, Pharmacia & Upjohn, Inc., Kalamazoo, MI 49007, USA.
      riqiang.yan@am.pnu.com
FAU - Bienkowski, M J
AU  - Bienkowski MJ
FAU - Shuck, M E
AU  - Shuck ME
FAU - Miao, H
AU  - Miao H
FAU - Tory, M C
AU  - Tory MC
FAU - Pauley, A M
AU  - Pauley AM
FAU - Brashier, J R
AU  - Brashier JR
FAU - Stratman, N C
AU  - Stratman NC
FAU - Mathews, W R
AU  - Mathews WR
FAU - Buhl, A E
AU  - Buhl AE
FAU - Carter, D B
AU  - Carter DB
FAU - Tomasselli, A G
AU  - Tomasselli AG
FAU - Parodi, L A
AU  - Parodi LA
FAU - Heinrikson, R L
AU  - Heinrikson RL
FAU - Gurney, M E
AU  - Gurney ME
LA  - eng
SI  - GENBANK/AF200342
SI  - GENBANK/AF200343
SI  - GENBANK/AF200344
SI  - GENBANK/AF200345
SI  - GENBANK/AF200346
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.45 (BACE2 protein, human)
RN  - EC 3.4.23.46 (BACE1 protein, human)
RN  - EC 3.4.23.46 (Bace1 protein, mouse)
SB  - IM
CIN - Nature. 1999 Dec 2;402(6761):471-2. PMID: 10591201
MH  - Alzheimer Disease/drug therapy/*enzymology
MH  - Amino Acid Sequence
MH  - Amyloid Precursor Protein Secretases
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Aspartic Acid Endopeptidases/antagonists & inhibitors/genetics/*metabolism
MH  - CHO Cells
MH  - Caenorhabditis elegans
MH  - Cell Line
MH  - Cell Membrane/enzymology
MH  - Cricetinae
MH  - Endopeptidases
MH  - Enzyme Inhibitors/therapeutic use
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oligonucleotides, Antisense/genetics/pharmacology
MH  - Recombinant Proteins/genetics/metabolism
MH  - Tissue Distribution
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1999/12/11 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/12/11 09:00
PHST- 1999/12/11 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/12/11 09:00 [entrez]
AID - 10.1038/990107 [doi]
PST - ppublish
SO  - Nature. 1999 Dec 2;402(6761):533-7. doi: 10.1038/990107.