Abstract
Antimicrobial peptides (AMPs) are classically known as important effector molecules in innate immunity across all multicellular organisms. However, emerging evidence begins to suggest multifunctional properties of AMPs beyond their antimicrobial activity, surprisingly including their roles in regulating neuronal function, such as sleep and memory formation. Aging, which is fundamental to neurodegeneration in both physiological and disease conditions, interestingly affects the expression pattern of many AMPs in an infection-independent manner. While it remains unclear whether these are coincidental events, or a mechanistic relationship exists, previous studies have suggested a close link between AMPs and a few key proteins involved in neurodegenerative diseases. This review discusses recent literature and advances in understanding the crosstalk between AMPs and the nervous system at both molecular and functional levels, with the aim to explore how AMPs may relate to neuronal vulnerability in aging.
Highlights
Antimicrobial peptides (AMPs) are short, typically cationic peptides that are found in every kingdom of life and were originally discovered as host defense peptides
Neuropeptides are an evolutionarily ancient and diverse set of messengers released from the nervous system that are critical in cell-to-cell signaling
It is tempting to speculate that AMPs may serve as the non-neuronal tissue analogues to neuropeptides to act as signaling molecules, mediators of the immune system, and neuromodulators
Summary
Antimicrobial peptides (AMPs) are short, typically cationic peptides that are found in every kingdom of life and were originally discovered as host defense peptides. As part of the innate immune system, AMPs fight off pathogens such as bacteria, fungi, parasites, and enveloped viruses, through their insertion and subsequent disruption of the membrane structure of microbe, or having interactions with microbial intracellular/intraviral components, or a combination of both (Raheem and Straus, 2019; Benfield and Henriques, 2020). Their ability to directly act upon and kill pathogens makes them an ideal target for use as therapeutic anti-infectives, and a potential alternative to traditional antibiotics, resulting in numerous rational design studies to create synthetic AMPs (Mahlapuu et al, 2016, 2020; Cardoso et al, 2020). We highlight and focus on recent advances in understanding the alternative roles of AMPs in the nervous system, within the context of aging and neurodegenerative diseases, and summarize the open questions of this rapidly expanding field
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