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Neuropeptides are a diverse class of neuronal signalling molecules that regulate physiological processes and behaviour in animals. However, determining the relationships and evolutionary origins of the heterogeneous assemblage of neuropeptides identified in a range of phyla has presented a huge challenge for comparative physiologists. Here, we review revolutionary insights into the evolution of neuropeptide signalling that have been obtained recently through comparative analysis of genome/transcriptome sequence data and by 'deorphanisation' of neuropeptide receptors. The evolutionary origins of at least 30 neuropeptide signalling systems have been traced to the common ancestor of protostomes and deuterostomes. Furthermore, two rounds of genome duplication gave rise to an expanded repertoire of neuropeptide signalling systems in the vertebrate lineage, enabling neofunctionalisation and/or subfunctionalisation, but with lineage-specific gene loss and/or additional gene or genome duplications generating complex patterns in the phylogenetic distribution of paralogous neuropeptide signalling systems. We are entering a new era in neuropeptide research where it has become feasible to compare the physiological roles of orthologous and paralogous neuropeptides in a wide range of phyla. Moreover, the ambitious mission to reconstruct the evolution of neuropeptide function in the animal kingdom now represents a tangible challenge for the future.
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http://dx.doi.org/10.1242/jeb.151092 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
The onset of puberty is increasingly observed at earlier ages in children, especially in girls with obesity, a trend that predisposes them to long-term metabolic and reproductive disorders in adulthood. Bile acids have emerged as pivotal signaling molecules in both metabolic and reproductive disorders, but remain unexplored in the early onset of puberty in children. Herein, we find elevated levels of muricholic acid (MCA) species in the serum of girls with central precocious puberty, which strongly correlate with indices of hypothalamic-pituitary-gonadal axis activation and can reach peak levels during puberty among healthy children.
View Article and Find Full Text PDFMediators Inflamm
September 2025
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Mast cells (MCs) are effectors of anaphylactoid reactions. Mas-related G-protein-coupled receptor X2 (MRGPRX2) receptor mediates the direct activation of MCs in anaphylactoid disease. Siglec-6 negatively regulates MC activation and is a promising target in the development of antianaphylactoid reaction drugs.
View Article and Find Full Text PDFImmunol Invest
September 2025
Respiratory and Critical Care Medicine, The 940th Hospital of Joint Logistics Support Force of chinese PLA, Lanzhou, China.
Background: Pulmonary neuroendocrine cells (PNECs) are specialized airway epithelial cells with dual sensory and secretory functions. They release bioactive mediators --including neuropeptides such as calcitonin gene-related peptide (CGRP) and gastrin-releasing peptide (GRP), and neurotransmitters such as 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) --that regulate airway smooth-muscle tone, mucus production, and immune responses. In chronic obstructive pulmonary disease (COPD), these PNEC-derived mediators contribute to airway inflammation, remodeling, and smooth-muscle dysfunction.
View Article and Find Full Text PDFNeuropsychopharmacology
September 2025
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Excessive alcohol use causes a great deal of harm and negative health outcomes. Corticotrophin releasing factor (CRF), a stress-related neuropeptide, has been implicated in binge ethanol intake and ethanol dependence in rodents. CRF containing neurons in the bed nucleus of the stria terminalis (BNST) can influence ethanol consumption.
View Article and Find Full Text PDFImmunity
September 2025
Institute for Infection Control and Prevention, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency (CCI), Medical Center and Fa
Resident macrophages play integral roles in maintaining tissue homeostasis and function. In the skin, prenatally seeded, specialized macrophages patrol sensory nerves and contribute to their regeneration after injury. However, mechanisms underlying the long-lasting postnatal commitment of these nerve-associated macrophages remain largely elusive.
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