Beyond Antimicrobial Defense: Insect Antimicrobial Peptides as Neuroimmune Effectors and Insect-Derived Peptide Resources.

Insect antimicrobial peptides (AMPs) are classically viewed as terminal effectors of innate immunity, but emerging evidence suggests that some can also shape defined neural states. In this Review, we argue that insect systems provide a powerful framework for resolving immune-brain communication at the level of individual peptide effectors, because genetically tractable innate-immune pathways allow pathway activation to be distinguished from peptide-specific effector function. Rather than surveying AMP families exhaustively, we focus on representative cases in which peptide identity, source, and timing can be linked to sleep, memory-related plasticity, and responses to acute injury. These studies show that the neural consequences of AMP induction cannot be inferred from pathway activation alone, but require peptide-level analysis of effector identity, cellular context, and exposure logic. This perspective also raises the question of translational potential. At present, direct biomedical development of endogenous insect AMPs in neural contexts remains limited, whereas more tangible applied interest has centered on insect venom peptides that share AMP-like physicochemical features. We therefore discuss insect venoms separately from endogenous AMP physiology. Venom peptides are not physiological equivalents of endogenous insect AMPs, but represent evolutionarily diversified AMP-like templates for scaffold discovery, mechanistic probing, and therapeutic engineering. Together, this review develops a peptide-level perspective on insect neuroimmune biology while highlighting insect venoms as a valuable, but highly constrained, source of templates for biomedical discovery.