Evolution of neuropeptides: from diffusing molecules to modulators of synaptic transmission
Neuropeptides are evolutionarily ancient signaling molecules that predate neurons and the central nervous system, yet they now function as powerful regulators of physiology and complex behavior. This review proposes that their success derives from a spectrum of “modes of action,” ranging from free d...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 2026
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| In: |
Progress in neurobiology
Year: 2026, Volume: 262, Pages: 1-15 |
| ISSN: | 1873-5118 |
| DOI: | 10.1016/j.pneurobio.2026.102920 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.pneurobio.2026.102920 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0301008226000468 
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| Author Notes: | Félix Leroy, Pablo Gimenez, Quirin Krabichler, Valery Grinevich |
| Summary: | Neuropeptides are evolutionarily ancient signaling molecules that predate neurons and the central nervous system, yet they now function as powerful regulators of physiology and complex behavior. This review proposes that their success derives from a spectrum of “modes of action,” ranging from free diffusion and volume transmission in early metazoans to more spatially restricted, circuit-specific modulation in bilaterians and vertebrates. In cnidarians, decentralized nerve nets still use peptidergic volume transmission to coordinate motor programs and behavioral plasticity, consistent with the idea that diffuse peptide signaling preceded synaptic wiring. As nervous systems centralized (e.g., tunicates, cephalochordates), neuropeptide families expanded and signaling became compartmentalized. In vertebrates, the blood-brain barrier and hypothalamo-pituitary axis enabled dual roles: endocrine hormones in the periphery and neuromodulators in the brain. The review argues that diffusion through the cerebrospinal fluid and focal axonal/dendritic release are complementary, with functional specificity determined by release site and receptor distribution. Neuropeptides also co-act with monoamines and fast amino-acid transmitters via co-release and pre-/post-synaptic modulation, providing layered control across timescales. Emerging biosensors and modern circuit tools are positioned to resolve peptide spatiotemporal dynamics and accelerate translational opportunities despite delivery constraints. |
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| Item Description: | Online verfügbar: 25. April 2026, Artikelversion: 4. Mai 2026 Gesehen am 25.06.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1873-5118 |
| DOI: | 10.1016/j.pneurobio.2026.102920 |