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.

Key words::

• Alzheimer’s disease
• GLP-1
• Huntington’s disease
• Neurodegenerative
• Parkinson’s disease
• Protection

Transparency

Declaration of funding

This study was funded by Novo Nordisk Inc.

Declaration of financial/other relationships

J.H. has disclosed that he is a consultant for Novo Nordisk and has spoken at sponsored scientific meetings. R.B. has disclosed that he has no relevant financial relationships to disclose. E.N. has disclosed that she is an employee of Watermeadow Medical.

CMRO peer reviewers have disclosed that they no relevant financial relationships to disclose.

Acknowledgments

The author takes full responsibility for this paper but is grateful to Watermeadow Medical for writing assistance, which was funded by Novo Nordisk Inc.