Peptide discovery across the spectrum of neuroinflammation; microglia and astrocyte phenotypical targeting, mediation, and mechanistic understanding

Abstract

Uncontrolled and chronic inflammatory states in the Central Nervous System (CNS) are the hallmark of neurodegenerative pathology and every injury or stroke-related insult. The key mediators of these neuroinflammatory states are glial cells known as microglia, the resident immune cell at the core of the inflammatory event, and astroglia, which encapsulate inflammatory insults in proteoglycan-rich scar tissue. Since the majority of neuroinflammation is exclusively based on the responses of said glia, their phenotypes have been identified to be on an inflammatory spectrum encompassing developmental, homeostatic, and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation. Recently, research groups have focused on peptide discovery to identify these phenotypes, find novel mechanisms, and mediate or re-engineer their actions. Peptides retain the diverse function of proteins but significantly reduce the activity dependence on delicate 3D structures. Several peptides targeting unique phenotypes of microglia and astroglia have been identified, along with several capable of mediating deleterious behaviors or promoting beneficial outcomes in the context of neuroinflammation. A comprehensive review of the peptides unique to microglia and astroglia will be provided along with their primary discovery methodologies, including top-down approaches using known biomolecules and naïve strategies using peptide and phage libraries.