TY - JOUR

T1 - The role of GLP-1 in neuronal activity and neurodegeneration

AU - Hölscher, Christian

N1 - Copyright © 2010 Elsevier Inc. All rights reserved.

PY - 2010

Y1 - 2010

N2 - Type 2 diabetes has been identified as a risk factor for Alzheimer's disease (AD). The underlying mechanism behind this unexpected link is most likely linked to the observed desensitization of insulin receptors in the brain. Insulin acts as a growth factor in the brain and supports neuronal repair, dendritic sprouting, and differentiation. Several drugs have been developed to treat type 2 diabetes which re-synthesize insulin receptors and may be of use to prevent neurodegenerative developments in AD. The incretin glucagon-like peptide-1 (GLP-1) is a hormone that facilitates insulin release under high blood sugar conditions. Interestingly, GLP-1 also has very similar growth factor like properties as insulin, and has been shown to protect neurons from toxic effects. In preclinical studies, GLP-1 and longer lasting analogues reduce apoptosis, protect neurons from oxidative stress, induce neurite outgrowth, protect synaptic plasticity and memory formation from the detrimental effects of β-amyloid, and reduce plaque formation and the inflammation response in the brains of mouse models of AD. An advantage of GLP-1 is that it does not affect blood sugar levels in nondiabetic people. Furthermore, recent research has shown that some GLP-1 analogues can cross the blood-brain barrier, including two that are on the market as a treatment for type 2 diabetes. Therefore, GLP-1 analogues show great promise as a novel treatment for AD or other neurodegenerative conditions.

AB - Type 2 diabetes has been identified as a risk factor for Alzheimer's disease (AD). The underlying mechanism behind this unexpected link is most likely linked to the observed desensitization of insulin receptors in the brain. Insulin acts as a growth factor in the brain and supports neuronal repair, dendritic sprouting, and differentiation. Several drugs have been developed to treat type 2 diabetes which re-synthesize insulin receptors and may be of use to prevent neurodegenerative developments in AD. The incretin glucagon-like peptide-1 (GLP-1) is a hormone that facilitates insulin release under high blood sugar conditions. Interestingly, GLP-1 also has very similar growth factor like properties as insulin, and has been shown to protect neurons from toxic effects. In preclinical studies, GLP-1 and longer lasting analogues reduce apoptosis, protect neurons from oxidative stress, induce neurite outgrowth, protect synaptic plasticity and memory formation from the detrimental effects of β-amyloid, and reduce plaque formation and the inflammation response in the brains of mouse models of AD. An advantage of GLP-1 is that it does not affect blood sugar levels in nondiabetic people. Furthermore, recent research has shown that some GLP-1 analogues can cross the blood-brain barrier, including two that are on the market as a treatment for type 2 diabetes. Therefore, GLP-1 analogues show great promise as a novel treatment for AD or other neurodegenerative conditions.

KW - Alzheimer Disease

KW - Animals

KW - Blood-Brain Barrier

KW - Diabetes Mellitus, Type 2

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Nerve Degeneration

KW - Receptor, Insulin

U2 - 10.1016/B978-0-12-381517-0.00013-8

DO - 10.1016/B978-0-12-381517-0.00013-8

M3 - Journal article

C2 - 21094907

VL - 84

SP - 331

EP - 354

JO - Vitamins and Hormones

JF - Vitamins and Hormones

SN - 0083-6729

ER -