Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer's disease?
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 MESSAGES Insulin-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.
a Department of Clinical Nutrition , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany.|b Department of Endocrinology, Diabetes and Nutrition , Campus Benjamin Franklin, Charité University Medicine , Berlin , Germany.|c German Center for Diabetes Research (DZD) , München , Germany.
Olga
O
Pivovarova
c German Center for Diabetes Research (DZD) , München , Germany.|d Department of Molecular Toxicology , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany.
Annika
A
Höhn
c German Center for Diabetes Research (DZD) , München , Germany.|d Department of Molecular Toxicology , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany.|e German Center for Cardiovascular Research (DZHK) , Berlin , Germany.
Tilman
T
Grune
a Department of Clinical Nutrition , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany.|b Department of Endocrinology, Diabetes and Nutrition , Campus Benjamin Franklin, Charité University Medicine , Berlin , Germany.|c German Center for Diabetes Research (DZD) , München , Germany.
Andreas F H
AF
Pfeiffer
a Department of Clinical Nutrition , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany.|b Department of Endocrinology, Diabetes and Nutrition , Campus Benjamin Franklin, Charité University Medicine , Berlin , Germany.|c German Center for Diabetes Research (DZD) , München , Germany.
Natalia
N
Rudovich
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007339:Insulysin / Q000037:antagonists & inhibitors*; D051379:Mice; D058990:Molecular Targeted Therapy
D004791:Enzyme Inhibitors; D007339:Insulysin
Alzheimer’s disease; insulin-degrading enzyme; type 2 diabetes