title: The nature, significance, and glucagon-like peptide-1 analog treatment of brain insulin resistance in Alzheimer's disease.
abstract: 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→insulin 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 Aβ. 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.
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: talbotk@cshs.org.
authors: Konrad
authors: K
authors: Talbot
authors: Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY, USA.
authors: Hoau-Yan
authors: HY
authors: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance
chemical_list: D052216:Glucagon-Like Peptide 1
keywords: Alzheimer's disease; Glucagon-like peptide-1; Hippocampus; Inflammation; Insulin receptor; Insulin receptor substrate-1; Insulin signaling; Liraglutide; Streptozotocin; Type 3 diabetes