PMID- 16432203
OWN - NLM
STAT- MEDLINE
DCOM- 20060321
LR  - 20240505
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 103
IP  - 5
DP  - 2006 Jan 31
TI  - An early specific cell-cell interaction occurs in the production of beta-amyloid 
      in cell cultures.
PG  - 1540-5
AB  - We have earlier proposed that a cell-cell interaction, mediated by the specific 
      binding of molecules of the beta-amyloid precursor protein (beta-APP) on one cell 
      surface with molecules of presenilin (PS) on the other cell surface, is a 
      required initial step in the ultimate production of beta-amyloid (Abeta) from 
      beta-APP. Abeta is widely believed to be the neurotoxic agent in Alzheimer's 
      disease. In this paper, we test this proposal by modifying cells to express 
      surface beta-APP but no PS, and other cells to express surface PS but no 
      beta-APP. Coculturing these two cell populations at appropriate cell densities 
      produces substantial amounts of Abeta that appear both in cell extracts and 
      culture media. Such Abeta production could occur only if the two cell types 
      interacted with one another to provide the beta-APP and the PS required for the 
      generation of Abeta. The addition to the coculture, from the start, of the 
      soluble specific N-terminal domain of the appropriate PS significantly reduces 
      the amount of Abeta produced. These and related experiments, therefore, suggest a 
      very different mechanism for Abeta production than the one that is currently 
      widely accepted.
FAU - Dewji, Nazneen N
AU  - Dewji NN
AD  - Department of Medicine and Stein Institute for Research on Aging, School of 
      Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 
      92093, USA. ndewji@ucsd.edu
FAU - Mukhopadhyay, Debashis
AU  - Mukhopadhyay D
FAU - Singer, S Jonathan
AU  - Singer SJ
LA  - eng
GR  - 5R01 NS 27580/NS/NINDS NIH HHS/United States
GR  - P30 NS047101/NS/NINDS NIH HHS/United States
GR  - P30 NS 047101/NS/NINDS NIH HHS/United States
GR  - R01 NS044768/NS/NINDS NIH HHS/United States
GR  - 5R01 AG 17858/AG/NIA NIH HHS/United States
GR  - 5R01 NS 044768/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060123
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
SB  - IM
MH  - Alzheimer Disease/metabolism
MH  - Amyloid beta-Peptides/*chemistry
MH  - Animals
MH  - Antibodies, Monoclonal/chemistry
MH  - Cell Communication
MH  - Cell Membrane/metabolism
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Embryo, Mammalian/cytology
MH  - Humans
MH  - Immunoprecipitation
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Fluorescence
MH  - Neurodegenerative Diseases
MH  - Neurons/metabolism
MH  - Presenilin-1
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Transfection
PMC - PMC1345709
EDAT- 2006/01/25 09:00
MHDA- 2006/03/22 09:00
PMCR- 2006/01/31
CRDT- 2006/01/25 09:00
PHST- 2006/01/25 09:00 [pubmed]
PHST- 2006/03/22 09:00 [medline]
PHST- 2006/01/25 09:00 [entrez]
PHST- 2006/01/31 00:00 [pmc-release]
AID - 0509899103 [pii]
AID - 1540 [pii]
AID - 10.1073/pnas.0509899103 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1540-5. doi: 
      10.1073/pnas.0509899103. Epub 2006 Jan 23.