title: Neuroprotective properties of GLP-1: theoretical and practical applications.
abstract: In the past few years, the development of pharmaceutical agents that enhance the physiological effects of glucagon-like peptide-1 (GLP-1), either through GLP-1 receptor agonism (GLP-1 agonists) or by inhibiting GLP-1 degradation (dipeptidylpeptidase-4 inhibitors) has broadened the range of treatment options for individuals with type 2 diabetes. It has been recognized for some time that GLP-1 also has extra-pancreatic effects, notably targeting the brain, where it regulates appetite and satiety, as well as peripheral functions highly controlled by the autonomic nervous system, such as gastric emptying. Furthermore, data are beginning to emerge that indicate a potential role for GLP-1 in neuroprotection. The increased risk of Alzheimer's disease, Parkinson's disease and stroke in people with type 2 diabetes suggests that shared mechanisms/pathways of cell death, possibly related to insulin dysregulation, may underlie all of these disorders. Although the disease anatomy varies with each disorder, a wide range of genetic and environmental triggers result in activation of similar biochemical pathways in all of them, suggesting a complex network of biochemical events that feed in to a final common path towards cellular dysfunction and death. This article summarizes the evidence for neuronal activity of GLP-1 and examines the limited data that currently exist on the therapeutic potential of GLP-1 in specific neurological and neurodegenerative conditions, namely Alzheimer's disease, Parkinson's disease, Huntingdon's disease, stroke and peripheral sensory neuropathy.
authors.affiliation: Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. jjholst@sund.ku.dk
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Remy
authors.initials: R
authors.lastname: Burcelin
authors.forename: Esther
authors.initials: E
authors.lastname: Nathanson
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000188:drug therapy / Q000209:etiology; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D009420:Nervous System / Q000187:drug effects*; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D052216:Glucagon-Like Peptide 1