Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging

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.

Single-nucleus sequencing of silkworm larval brain reveals the key role of lysozyme in the antiviral immune response in brain hemocytes

“…5 d), even in the noninfected condition, in contrast to hemocytes from the hemolymph where only the expression of cecropins is observed [ 18 , 37 ]. This observation is consistent with additional functional roles for AMPs in neuronal function and development that were revealed more recently [ 58 , 59 ]. AMPs have structural similarities with neuropeptides and some of the latter exhibit antimicrobial activity [ 60 ].…”

“…In Drosophila , long-term memory is modulated by neuronally expressed AMPs [ 61 ]. AMPs are also speculated to have important roles in neurodegeneration and Alzheimer’s disease in humans [ 58 , 59 ]. From this point of view, we are more inclined to believe that the hemocyte-like cells of cluster 12 represent brain-specific resident macrophages that regulate neuron function and homeostasis through the expression of AMPs.…”

Downregulation of oxidative stress-mediated glial innate immune response suppresses seizures in a fly epilepsy model

“…Alternatively, AMPs might act as actual signaling molecules in order to exert their neurodegenerative/neuronal cell death effects through receptor (G-protein-coupled receptor/tyrosine kinase/ligand-gated ion channel-mediated autophagy or apoptosis. 99 …”

Unraveling the Role of Antimicrobial Peptides in Insects

“…In addition, the insect nervous system can mount a local immune response to infection, and activation of signaling pathways may lead to neurodegeneration, malfunctioning neurons, and altered behavior [ 23 ]. Moreover, the AMP expression pattern is affected by aging independently of infection, and it has been postulated that an increased level of some AMPs produced in non-neuronal tissues during aging can mediate a signal initiating neuronal aging [ 24 ].…”