Concise Overview of Glypromate Neuropeptide Research: From Chemistry to Pharmacological Applications in Neurosciences

Neurodegenerative diseases of the central nervous system (CNS) pose a serious health concern worldwide, with a particular incidence in developed countries as a result of life expectancy increase and the absence of restorative treatments. Presently, treatments for these neurological conditions are focused on managing the symptoms and/or slowing down their progression. As so, the research on novel neuroprotective drugs is of high interest. Glypromate (glycyl-L-prolyl-L-glutamic acid, also known as GPE), an endogenous small peptide widespread in the brain, holds great promise to tackle neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's, s well as other CNS-related disorders like Rett and Down's syndromes. However, the limited pharmacokinetic properties of Glypromate hinder its clinical application. As such, intense research has been devoted to leveraging the pharmacokinetic profile of this neuropeptide. This review aims to offer an updated perspective on Glypromate research by exploring the vast array of chemical derivatizations of more than 100 analogs described in the literature over the past two decades. The collection and discussion of the most relevant structure-activity relationships will hopefully guide the discovery of new Glypromate-based neuroprotective drugs.

Automated summary

Neurodegenerative diseases of the central nervous system (CNS) are a global health concern, especially in developed countries due to increased life expectancy and the lack of restorative treatments. Glypromate, a brain-derived peptide, shows promise in treating these diseases, but its limited pharmacokinetic properties hinder its clinical application. This review explores the chemical derivatizations of more than 100 analogs of Glypromate and their structure-activity relationships, aiming to guide the discovery of new Glypromate-based neuroprotective drugs.