Research

Several neuroactive peptides are being investigated for their ability to support cognition, stress resilience, and neuroprotection. Semax, an ACTH(4-7) analogue extended with Pro-Gly-Pro—has repeatedly shown transcriptional up-regulation of neurotrophins (BDNF/NGF) and their receptors after cerebral ischemia, alongside modulation of immune/inflammatory gene programs in brain tissue [1,2]. These transcriptomic and protein-level shifts map to processes central to synaptic plasticity and recovery from injury.

Selank, a heptapeptide derived from tuftsin, has been studied for anxiolytic and nootropic potential via effects on neurotransmission. In vivo work shows Selank alters the expression of GABAergic and broader neurotransmission genes in frontal cortex within hours of dosing, supporting a mechanism that includes positive allosteric modulation of GABA receptors and downstream stabilization of stress-linked signaling [3,4].

Finally, reproductive-neuropeptide signaling is increasingly linked to emotional processing. Kisspeptin, best known for initiating GnRH/LH release, has also been shown in humans to enhance limbic brain activity to sexual and bonding stimuli and to attenuate negative mood during controlled infusion, demonstrating a bridge between endocrine control and affective brain circuits [5,6]. Together, these lines of research highlight peptide pathways that converge on neurotrophin support, inhibitory tone (GABA), and limbic network modulation, offering routes for future neuroprotective and mood-focused investigation.

References

1. Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010;30(1):71–79. PMID: 19633950 | PMCID: PMC11498467

2. Sudarkina OY, et al. Brain protein expression profile confirms the protective effect of the ACTH(4–7)PGP peptide (Semax) in a rat model of cerebral ischemia–reperfusion. Int J Mol Sci. 2021;22(13):7030. PMID: 34201112 | PMCID: PMC8226508

3. Volkova A, et al. Selank administration affects the expression of some genes involved in GABAergic neurotransmission. Front Pharmacol. 2016;7:31. PMID: 26924987 | PMCID: PMC4757669

4. Vyunova TV, et al. Peptide-based anxiolytics: the molecular aspects of heptapeptide Selank biological activity.Protein Pept Lett. 2018;25(10):914–923. PMID: 30255741

5. Comninos AN, et al. Kisspeptin modulates sexual and emotional brain processing in humans. J Clin Invest.2017;127(2):709–719. PMID: 28112678 | PMCID: PMC5272173

6. Comninos AN, et al. Emerging roles of kisspeptin in sexual and emotional brain processing. Neuroendocrinology.2018;106(2):195–206. PMID: 28866668