PMID- 10702374
OWN - NLM
STAT- MEDLINE
DCOM- 20000512
LR  - 20190831
IS  - 1093-9946 (Print)
IS  - 1093-4715 (Linking)
VI  - 5
DP  - 2000 Jan 1
TI  - Cellular and molecular basis of beta-amyloid precursor protein metabolism.
PG  - D72-83
AB  - In molecular neurobiology, perhaps no molecule has been as thoroughly examined as 
      Alzheimer's beta-amyloid precursor protein (beta-APP). In the years since the 
      cDNA encoding beta-APP was cloned, the protein has been the subject of 
      unparalleled scrutiny on all levels. From molecular genetics and cellular biology 
      to neuroanatomy and epidemiology, no scientific discipline has been left 
      unexplored - and with good reason. beta-amyloid (Abeta) is the main constituent 
      of the amyloidogenic plaques which are a primary pathological hallmark of 
      Alzheimer's disease, and bta-APP is the protein from which Abeta is cleaved and 
      released. Unraveling the molecular events underlying Abeta generation has been, 
      and remains, of paramount importance to scientists in our field. In this review 
      we will trace the progress that has been made in understanding the molecular and 
      cellular basis of beta-APP trafficking and processing, or alternatively stated, 
      the molecular basis for Abeta generation. Imperative to a complete understanding 
      of Abeta generation is the delineation of its subcellular localization and the 
      identification of proteins that play either direct or accessory roles in Abeta 
      generation. We will focus on the regulation of beta-APP cleavage through diverse 
      signal transduction mechanisms and discuss possible points of therapeutic 
      intercession in what has been postulated to be a seminal molecular step in the 
      cascade of events terminating in the onset of dementia, loss of neurons, and 
      eventual death from Alzheimer's disease.
FAU - Greenfield, J P
AU  - Greenfield JP
AD  - Fisher Center for Alzheimer Research and Laboratory of Molecular and Cellular 
      Neuroscience, The Rockefeller University, New York NY 10021, USA.
FAU - Gross, R S
AU  - Gross RS
FAU - Gouras, G K
AU  - Gouras GK
FAU - Xu, H
AU  - Xu H
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20000101
PL  - United States
TA  - Front Biosci
JT  - Frontiers in bioscience : a journal and virtual library
JID - 9709506
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN2 protein, human)
RN  - 0 (Presenilin-2)
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)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid Precursor Protein Secretases
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/chemistry/*metabolism
MH  - Animals
MH  - Aspartic Acid Endopeptidases/genetics/metabolism
MH  - Endopeptidases
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Presenilin-2
RF  - 115
EDAT- 2000/03/07 09:00
MHDA- 2000/05/20 09:00
CRDT- 2000/03/07 09:00
PHST- 2000/03/07 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 2000/03/07 09:00 [entrez]
AID - 10.2741/greenfield [doi]
PST - epublish
SO  - Front Biosci. 2000 Jan 1;5:D72-83. doi: 10.2741/greenfield.