Aging-related correlation of insulin-degrading enzyme with gamma-secretase-generated products involving insulin and glucose levels in transgenic mice.
Insulin-degrading enzyme (IDE) is a 110-kDa thiol zinc-methalloendopeptidase that can cleave small Abeta peptides and the APP intracellular domain (AICD). The aim of this study was to examine aging-related correlation of IDE with gamma-secretase-generated products involving insulin and glucose levels in transgenic brains expressing neuron-specific enolase (NSE)-controlled human mutant presenilin-2 (hPS2m). Herein, we concluded that the levels of IDE expression in transgenic brains were decreased relative to those of control mice at 15 months of age. In parallel, inhibition in the IDE expression at this age underlies to the levels-up of Abeta-42, AICD, gamma-secretase, and glucose with a level-down of insulin. Thus, IDE expression is critical target for the therapeutic trials.
Hwang
Dae Y
DY
Division of Laboratory Animal Resources, , National Institute of Toxicological Research, Korea FDA, Seoul, 122-704, Korea.
Cho
Jung S
JS
Kim
Chuel K
CK
Shim
Sun B
SB
Jee
Seung W
SW
Lee
Su H
SH
Seo
Su J
SJ
Cho
Joon Y
JY
Lee
Seok H
SH
Kim
Yong K
YK
D000375:Aging / Q000502:physiology*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007339:Insulysin / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D053766:Presenilin-2
D016229:Amyloid beta-Peptides; D001786:Blood Glucose; D007328:Insulin; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053766:Presenilin-2; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse; D007339:Insulysin; D010751:Phosphopyruvate Hydratase