The nature, significance, and glucagon-like peptide-1 analog treatment of brain insulin resistance in Alzheimer's disease

详细信息    查看全文

• 作者：Konrad Talbot ; Hoau-Yan Wang
• 关键词：Alzheimer's disease ; Glucagon-like peptide-1 ; Inflammation ; Insulin receptor ; Insulin receptor substrate-1 ; Insulin signaling ; Hippocampus ; Liraglutide ; Streptozotocin ; Type 3 diabetes
• 刊名：Alzheimer's Dementia
• 出版年：February, 2014
• 年：2014
• 卷：10
• 期：1_supp_S
• 页码：S12-S25
• 全文大小：1736 K

文摘

Alzheimer's disease (AD) is an age-related neurodegenerative disease leading over the course of decades to the most common form of dementia. Many of its pathologic features and cognitive deficits may be due in part to brain insulin resistance recently demonstrated in the insulin receptor鈫抜nsulin receptor substrate-1 (IRS-1) signaling pathway. The proximal cause of such resistance in AD dementia and amnestic mild cognitive impairment (aMCI) appears to be serine inhibition of IRS-1, a phenomenon likely due to microglial release of inflammatory cytokines triggered by oligomeric A尾. Studies on animal models of AD and on human brain tissue from MCI cases at high risk of AD dementia have shown that brain insulin resistance and many other pathologic features and symptoms of AD may be greatly reduced or even reversed by treatment with FDA-approved glucagon-like peptide-1 (GLP-1) analogs such as liraglutide (Victoza). These findings call attention to the need for further basic, translational, and clinical studies on GLP-1 analogs as promising AD therapeutics.