TY - JOUR

T1 - Neuroprotective properties of GLP-1

T2 - theoretical and practical applications

AU - Holst, Jens Juul

AU - Burcelin, Remy

AU - Nathanson, Esther

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Animals

KW - Diabetes Complications

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Models, Biological

KW - Models, Theoretical

KW - Nervous System

KW - Nervous System Diseases

KW - Neuroprotective Agents

U2 - 10.1185/03007995.2010.549466

DO - 10.1185/03007995.2010.549466

M3 - Journal article

C2 - 21222567

VL - 27

SP - 547

EP - 558

JO - Current Medical Research and Opinion, Supplement

JF - Current Medical Research and Opinion, Supplement

SN - 0141-9951

IS - 3

ER -