PMID- 19387119
OWN - NLM
STAT- MEDLINE
DCOM- 20090707
LR  - 20171116
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 16
IP  - 4
DP  - 2009
TI  - Regulated proteolysis of RAGE and AbetaPP as possible link between type 2 
      diabetes mellitus and Alzheimer's disease.
PG  - 865-78
LID - 10.3233/JAD-2009-0998 [doi]
AB  - Epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an 
      increased risk of developing Alzheimer's disease (AD). In T2DM, the elevated 
      blood glucose level promotes formation of advanced glycation end products (AGEs). 
      The receptor for AGEs (RAGE) is a type I membrane-protein and is also able to 
      import amyloid-beta (Abeta) from the blood across the blood-brain-barrier into 
      the brain. Oligomeric Abeta peptides disturb synaptic function in the brain and 
      are believed to contribute to the development of AD. Abeta peptides are released 
      from the amyloid-beta protein precursor (AbetaPP) after sequential proteolysis by 
      beta- and gamma-secretases but alpha-secretase-mediated cleavage of AbetaPP 
      prevents Abeta generation. Insulin influences Abeta production by modulating 
      alpha-secretase activity and Abeta degradation. Recent publications demonstrate 
      that RAGE is subjected to protein ectodomain shedding. Proteolysis of RAGE occurs 
      constitutively and is inducible by activation of protein kinase C. 
      Alpha-secretase-like enzymes release the ligand binding domain of RAGE from the 
      cell surface and after that gamma-secretase processes the membrane-remaining part 
      of RAGE. Proteolysis of RAGE may represent a regulatory mechanism in RAGE signal 
      transduction and in addition may prevent Abeta peptide transport across the 
      blood-brain-barrier. Current data suggest that the sequential proteolysis of RAGE 
      is homologous to AbetaPP processing.
FAU - Kojro, Elzbieta
AU  - Kojro E
AD  - Institute of Biochemistry, Johannes Gutenberg University Mainz, Mainz, Germany. 
      kojro@uni-mainz.de
FAU - Postina, Rolf
AU  - Postina R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Alzheimer Disease/etiology/*metabolism
MH  - Amyloid Precursor Protein Secretases/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Cholesterol/metabolism
MH  - Diabetes Mellitus, Type 2/etiology/*metabolism
MH  - Humans
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/*metabolism
RF  - 122
EDAT- 2009/04/24 09:00
MHDA- 2009/07/08 09:00
CRDT- 2009/04/24 09:00
PHST- 2009/04/24 09:00 [entrez]
PHST- 2009/04/24 09:00 [pubmed]
PHST- 2009/07/08 09:00 [medline]
AID - Q1H7RW615R085V01 [pii]
AID - 10.3233/JAD-2009-0998 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2009;16(4):865-78. doi: 10.3233/JAD-2009-0998.