Targeting amyloid-beta by glucagon-like peptide-1 (GLP-1) in Alzheimer's disease and diabetes

被引：33

作者：

Bak, Ann Mosegaard ^{[1
]}

Egefjord, Laerke ^{[2
]}

Gejl, Michael ^{[2
]}

Steffensen, Charlotte ^{[1
]}

Stecher, Chalotte Willemann ^{[3
]}

Smidt, Kamille ^{[2
]}

Brock, Birgitte ^{[4
]}

Rungby, Jorgen ^{[2
]}

机构：

[1] Aarhus Univ Hosp, Dept Med Endocrinol, MEA, DK-8000 Aarhus C, Denmark

[2] Univ Aarhus, Dept Pharmacol, DK-8000 Aarhus C, Denmark

[3] Aarhus Univ Hosp, Dept Infect Dis, DK-8200 Aarhus N, Denmark

[4] Aarhus Univ Hosp, Dept Clin Pharmacol, DK-8000 Aarhus, Denmark

来源：

EXPERT OPINION ON THERAPEUTIC TARGETS | 2011年 / 15卷 / 10期

关键词：

Alzheimer's disease; amyloid; beta amyloid; diabetes; GLP-1; IAPP; SYNAPTIC PLASTICITY; PRECURSOR PROTEIN; NEURONAL-ACTIVITY; ENDOGENOUS GLP-1; RODENT MODELS; ANIMAL-MODEL; PC12; CELLS; INSULIN; RECEPTOR; BRAIN;

D O I：

10.1517/14728222.2011.600691

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Introduction: Epidemiological evidence suggests an association between type 2 diabetes (T2DM) and Alzheimer's disease (AD), in that one disease increases the risk of the other. T2DM and AD share several molecular processes which underlie the tissue degeneration in either disease. Disturbances in insulin signaling may be the link between the two conditions. Drugs originally developed for T2DM are currently being considered as possible novel agents in the treatment of AD. Areas covered: This review discusses the potential role of glucagon-like peptide -1 (GLP-1) treatment in AD. GLP-1 receptors are expressed in areas of the brain important to memory and learning, and GLP-1 has growth-factor-like properties similar to insulin. A key neuropathological feature of AD is the accumulation of amyloid-beta (Ab). In preclinical studies, GLP-1 and longer lasting analogues have been shown to have both neuroprotective and neurotrophic effects, and to protect synaptic activity in the brain from Ab toxicity. Expert opinion: A convincing amount of evidence has shown a beneficial effect of GLP-1 agonist treatment on cognitive function, memory and learning in experimental models of AD. GLP-1 analogues may therefore be the new therapeutic agent of choice for intervention in AD.

引用

页码：1153 / 1162

页数：10

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