Transcriptomic Insights Into the Evolution of Snake Venom: Mechanisms, Diversity, and Adaptation

  Transcriptomic Insights Into the Evolution of Snake Venom: Mechanisms, Diversity, and Adaptation Abstract Snake venoms are evolutionarily refined biochemical arsenals composed of diverse toxins with complex functional roles in predation, defense, and competition. Over the past 2 decades, transcriptomic approaches have transformed venom research by enabling high-resolution insights into gene expression dynamics, molecular diversity, and the evolutionary mechanisms driving venom variation across lineages. In this review, we present a comprehensive synthesis of snake venom transcriptomics literature and propose a conceptual framework structured around three major axes: (1) gene family expansion through duplication and neofunctionalization; (2) regulatory complexity encompassing transcriptional, posttranscriptional, and epigenetic modulation; and (3) ecological selection pressures shaping venom profiles in response to diet, habitat, and interspecific interactions. We integrate findin...

Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice

 


Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice

Abstract

We evaluated the effects of Tetrascorpin-1 from Androctonus australis (AaTs-1), a tetrapeptide obtained from scorpion venom, previously hypothesized to bind the formyl peptide receptor like-1 (FPRL-1) known as formyl peptide receptor-2 (FPR-2) in vitro, on pain responses and cytokines, neuronal and glial morpho-functional alterations in the spinal cord of mice with formalin-induced long-lasting pain hypersensitivity. Due to the peptide chemical nature and for favoring its penetration into the central nervous system, AaTs-1 was daily administered intranasally for 10 days. In formalin-injected mice the AaTs-1 treatment abolished mechanical allodynia, thermal hyperalgesia, hyperactivation of spinal nociceptive-specific (NS) neurons, and partially restored spinal anti-inflammatory/pro-inflammatory cytokine levels and microglia/astrocyte phenotype alterations. Additionally, in contrast to what occurred in formalin-injected mice, AaTs-1 treatment facilitated the firing activity of NS neurons and consistently altered the levels of some spinal cytokines under investigation in healthy mice. Based on the opposing effects of AaTs-1 under physiological and pathological conditions, we suspect that it acts as a partial agonist in vivo rather than as an antagonist of FPR-2, as other in vitro data would suggest.
Pagano, S., Limongelli, R., Moslah, W., Saada, M., Manzo, I., Bonsale, R., Teweldemedhin, M. M., Fusco, A., Guida, F., Belardo, C., Morace, A. M., Perrone, M., Ricciardi, F., Pierretti, G., Vastarella, M. G., Infantino, R., Srairi-Abid, N., Maione, S., Palazzo, E., . . . Luongo, L. (2025). Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice. Toxicon, 108611. https://doi.org/10.1016/j.toxicon.2025.108611