Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer's disease?

被引：92
|
作者：
Pivovarova, Olga [1 ,2 ,3 ]
Hoehn, Annika [3 ,4 ]
Grune, Tilman [3 ,4 ,5 ]
Pfeiffer, Andreas F. H. [1 ,2 ,3 ]
Rudovich, Natalia [1 ,2 ,3 ]
机构：
[1] German Inst Human Nutr Potsdam Rehbrucke, Dept Clin Nutr, Nuthetal, Germany
[2] Charite, Dept Endocrinol Diabet & Nutr, Campus Benjamin Franklin, Berlin, Germany
[3] German Ctr Diabet Res DZD, Munich, Germany
[4] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Toxicol, Nuthetal, Germany
[5] German Ctr Cardiovasc Res DZHK, Berlin, Germany
来源：
ANNALS OF MEDICINE | 2016年 / 48卷 / 08期
关键词：
Alzheimer's disease; insulin-degrading enzyme; type; 2; diabetes; AMYLOID BETA-PROTEIN; SMALL-MOLECULE ACTIVATORS; A-BETA; MOUSE MODEL; EXTRACELLULAR LEVELS; COGNITIVE DEFICITS; CONVERTING ENZYME; FACTOR EXPRESSION; IMPAIRED INSULIN; TRANSGENIC MICE;
D O I：
10.1080/07853890.2016.1197416
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Insulin-degrading enzyme (IDE) is a major enzyme responsible for insulin degradation. In addition to insulin, IDE degrades many targets including glucagon, atrial natriuretic peptide, and beta-amyloid peptide, regulates proteasomal degradation and other cell functions. IDE represents a pathophysiological link between type 2 diabetes (T2DM) and late onset Alzheimer's disease (AD). Potent and selective modulators of IDE activity are potential drugs for therapies of both diseases. Acute treatment with a novel IDE inhibitor was recently tested in a mouse study as a therapeutic approach for the treatment of T2DM. In contrast, effective IDE activators can be used for the AD treatment. However, because of the pleiotropic IDE action, the sustained treatment with systemic IDE modulators should be carefully tested in animal studies. Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets.KEY MESSAGESInsulin-degrading enzyme (IDE) represents a pathophysiological link between type 2 diabetes (T2DM) and Alzheimer's disease (AD).Selective modulators of IDE activity are potential drugs for both T2DM and AD treatment.Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets.
引用
收藏
页码：614 / 624
页数：11
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