Kisspeptin-10 peptide consists of 10 amino acids and has the sequence Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2. It shares the same C-terminal decapeptide sequence known as RFAmide (arginine-amidated phenylalanine) with the other processed kisspeptin sequences. Although Kisspeptin-10 has intrinsic bioactivity similar to the longer kisspeptin fragments, it is also been characterized by researchers to exhibit a shorter half-life and a more rapid onset of potential action.

Kisspeptin-10 Peptide and The Gonadotropic Axis

Kisspeptin-10 appears to potentially play a complex role in GnRH-producing hypothalamic cells. Researchers were investigating the potential impact of Kisspeptin-10 (KP-10) on gene expression in different types of hypothalamic cell lines.^[2] They suggested that in mHypoA-50 AVPV cells, Kisspeptin-10 may increase Kiss-1 mRNA and kisspeptin protein levels, possibly without affecting GnRH expression. In mHypoA-55 ARC cells, both kisspeptin genes and GnRH expression may be upregulated by Kisspeptin-10 peptide stimulation. Furthermore, Kisspeptin-10 appeared to elevate c-Fos protein levels, indicating potential neuronal activity in both cell lines. Similar apparent responses were observed in primary cultures of fetal rat neuronal cells.

Studies also suggest that Kisspeptin-10 may stimulate GnRH release in pre-pubescence and pubescence.^[3] Researchers have reported that there appeared to be a significant remodeling of the native kisspeptin and neurokinin B (NKB) signaling pathways when exposed to Kisspeptin-10. In fact, Kisspeptin-10 may interact with GnRH release via both NKB neurons and kisspeptin neurons. They also comment that there may be “a parallel increase in kisspeptin release and GnRH release during puberty.” Yet, the peptide did not appear to have any initiation potential regarding pubescence.

Researchers have also aimed to investigate the potential impact of Kisspeptin-10 on the production of progesterone (P4) in bovine granulosa cells (BGCs) and the role of microRNA 1246 (miR-1246) in this process.^[4] The scientists hypothesized that exposing BGCs to Kisspeptin-10 may increase the levels of P4, mRNA expression of the steroidogenesis-related gene StAR, and free cholesterol content. Simultaneously, it appeared to decrease the expression of miR-1246 in BGCs. Overexpressing miR-1246 may also inhibit P4 synthesis, StAR mRNA expression, and free cholesterol content in BGCs, while under-expressing miR-1246 may reverse this impact. Furthermore, overexpressing miR-1246 counteracted the enhancing potential of Kisspeptin-10 on P4 synthesis, StAR mRNA expression, and free cholesterol content in BGCs. Conversely, under-expressing miR-1246 appeared to amplify the enhancing potential of Kisspeptin-10. The study also indicated that miR-1246 targeted the 3’UTR of StAR in BGCs, suggesting that Kisspeptin-10 peptide promotes P4 synthesis in BGCs by facilitating the transport of free cholesterol through the regulation of miR-1246/StAR expression.

Kisspeptin-10 Peptide and Cholinergic Neurons

The accommodation of amyloid-β (Aβ) and α-synuclein (α-syn) in cholinergic neurons may potentially damage them. Yet, researchers suggest that Kisspeptin-10 may bind to Aβ extracellularly and thus potentially inhibit Aβ toxicity.^[5] The scientists comment that “The KP peptides inhibited the neurotoxicity of Aβ, PrP, and IAPP peptides, via an action that could not be blocked by kisspeptin-receptor (GPR-54) or neuropeptide FF (NPFF) receptor antagonists.” Based on similarities between α-syn’s non-amyloid-β component (NAC) and Aβ’s C-terminus, other researchers have also hypothesized that Kisspeptin-10 might also mitigate α-syn-induced toxicity in cholinergic neurons.^[6] They conducted experiments using cholinergic cells and commented that high concentrations of Kisspeptin-10 may increase toxicity, while low concentrations may potentially reduce both wild-type and E46K mutant α-syn-induced toxicity. The computational analysis supported these findings, indicating potentially favorable binding between Kisspeptin-10 and the C-terminal residues of α-syn. Molecular dynamics simulations also suggested the Kisspeptin-10-α-syn complexes had good stability. 

Scientists have continued to explore this topic, specifically whether GPR54 (the receptor for the kisspeptin gene) activation is necessary for the Kisspeptin-10 peptide binding potential to the C-terminal pockets of α-syn.^[7] To investigate this, ChAT-positive SH-SY5Y neurons were engineered to overexpress wild-type or E46K mutant α-syn, and the potential impact of Kisspeptin-10 on α-syn-induced neuronal death was evaluated using flow cytometry and immunocytochemistry. Kisspeptin-10 appeared to reduce apoptosis and mitochondrial damage caused by wild-type and E46K mutant α-syn in cholinergic neurons. Interestingly, the apparent neuroprotective potential of Kisspeptin-10 remained unaffected by combined presentation with a GPR54 antagonist, kisspeptin-234 (KP-234), indicating that GPR54 activation might not be essential for Kisspeptin-10’s action. Furthermore, the researchers commented that Kisspeptin-10 reduced α-syn and choline acetyltransferase (ChAT) immunoreactivity in neurons overexpressing wild-type and E46K mutant α-syn. 

Kisspeptin-10 Peptide and Orexigenic Stimuli

Scientists have aimed to explore the potential metabolic and orexigenic action of Kisspeptin-10peptide by examining its possible impact on gene expression of neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF), as well as the levels of dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxy indole acetic acid (5-HIIA) in hypothalamic cells (Hypo-E22).^[8] The results suggested that Hypo-E22 cells appear to tolerate Kisspeptin-10, and it may independently increase NPY gene expression, while BDNF expression appeared inhibited. Additionally, Kisspeptin-10 appeared to reduce 5-HT and DA levels, while NE levels reportedly remained unaffected. The apparent decrease in DA and 5-HT was consistent with increased ratios of DOPAC/DA and 5-HIIA/5-HT induced by the peptide. The apparent increase in NPY expression while reducing BDNF and 5-HT activity may support the orexigenic potential of  Kisspeptin-10.

Conclusion

In conclusion, Kisspeptin-10 peptide, derived from the cleavage of Kisspeptin-54, exhibits distinct characteristics compared to longer kisspeptin fragments. In vitro studies have shed light on its potential on the gonadotropic axis, cholinergic neurons, and orexigenic stimuli. Kisspeptin-10 appears to modulate gene expression and protein levels, potentially influencing neuronal activity and GnRH release. Moreover, it shows promise in mitigating the toxicity induced by amyloid-β and α-synuclein in cholinergic neurons. The peptide’s neuroprotective potential was observed independently of GPR54 activation, suggesting alternative mechanisms at play. Additionally, Kisspeptin-10 may impact gene expression and neurotransmitter levels related to its orexigenic potential.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

References

1. Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J. M., Le Poul, E., Brézillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., Blanpain, C., Schiffmann, S. N., Vassart, G., & Parmentier, M. (2001). The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. The Journal of biological chemistry, 276(37), 34631–34636. https://doi.org/10.1074/jbc.M104847200
2. Kanasaki, H., Tumurbaatar, T., Tumurgan, Z., Oride, A., Okada, H., & Kyo, S. (2021). Mutual Interactions Between GnRH and Kisspeptin in GnRH- and Kiss-1-Expressing Immortalized Hypothalamic Cell Models. Reproductive sciences (Thousand Oaks, Calif.), 28(12), 3380–3389. https://doi.org/10.1007/s43032-021-00695-z
3. Garcia, J. P., Keen, K. L., Seminara, S. B., & Terasawa, E. (2019). Role of Kisspeptin and NKB in Puberty in Nonhuman Primates: Sex Differences. Seminars in reproductive medicine, 37(2), 47–55. https://doi.org/10.1055/s-0039-3400253
4. Guo, L., Xu, H., Li, Y., Liu, H., Zhao, J., Lu, W., & Wang, J. (2022). Kisspeptin-10 Promotes Progesterone Synthesis in Bovine Ovarian Granulosa Cells via Downregulation of microRNA-1246. Genes, 13(2), 298. https://doi.org/10.3390/genes13020298
5. Milton NG, Chilumuri A, Rocha-Ferreira E, Nercessian AN, Ashioti M. Kisspeptin prevention of amyloid-β peptide neurotoxicity in vitro. ACS Chem Neurosci. 2012 Sep 19;3(9):706-19. doi: 10.1021/cn300045d. Epub 2012 May 30. PMID: 23019497; PMCID: PMC3447396.
6. Simon, C., Soga, T., Ahemad, N., Bhuvanendran, S., & Parhar, I. (2022). Kisspeptin-10 Rescues Cholinergic Differentiated SHSY-5Y Cells from α-Synuclein-Induced Toxicity In Vitro. International journal of molecular sciences, 23(9), 5193. https://doi.org/10.3390/ijms23095193
7. Simon, C., Soga, T., & Parhar, I. (2023). Kisspeptin-10 Mitigates α-Synuclein-Mediated Mitochondrial Apoptosis in SH-SY5Y-Derived Neurons via a Kisspeptin Receptor-Independent Manner. International journal of molecular sciences, 24(7), 6056. https://doi.org/10.3390/ijms24076056
8. Orlando, G., Leone, S., Ferrante, C., Chiavaroli, A., Mollica, A., Stefanucci, A., Macedonio, G., Dimmito, M. P., Leporini, L., Menghini, L., Brunetti, L., & Recinella, L. (2018). Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control. Molecules (Basel, Switzerland), 23(12), 3071. https://doi.org/10.3390/molecules23123071

Like Semax, N-Acetyl Semax peptide has been studied for its neuroprotective and nootropic potential.^[2] It is hypothesized to increase levels of neurotrophic factors in the brain, such as Brain-Derived Neurotrophic Factor (BDNF). BDNF is considered important for neurons’ growth, survival, and maintenance. Upregulation of BDNF levels may have neuroprotective potential and act favorably on higher cerebral functions.

N-Acetyl Semax and BDNF

N-Acetyl Semax may have the ability to activate and elevate the levels of neurotrophic factors in the central nervous system, such as the Brain-Derived Neurotrophic Factor (BDNF). One clinical trial aimed to investigate the potential of the peptide on plasma BDNF levels, motor performance, and Barthel index score after ischemic nerve damage.^[3] According to the research, N-acetyl Semax presentation may increase BDNF plasma levels, accelerate the improvement and final outcome of Barthel score index speed functional recovery, and support motor performance. Moreover, the researchers reported that “There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement.”

Another trial also suggests that N-Acetyl Semax may stimulate the synthesis of BDNF in astrocytes and potentially increase BDNF levels in the basal forebrain but not in the cerebellum.^[4] 

Apart from potentially increasing BDNF protein and mRNA levels in the central nervous system, some studies suggest that N-Acetyl Semax may also result in increased tyrosine phosphorylation levels of trkB.^[5] The researchers reported a “maximal 1.4-fold increase of BDNF protein levels accompanying with 1.6-fold increase of trkB tyrosine phosporylation levels, and a 3-fold and a 2-fold increase of exon III BDNF and trkB mRNA levels, respectively,” trkB (tropomyosin receptor kinase B) is a protein receptor found on the surface of certain neurons in the brain. It is the receptor for Brain-Derived Neurotrophic Factor (BDNF), which is considered by scientists to play an important role in neurons’ growth, survival, and maintenance. When BDNF binds to trkB, it appears to trigger a series of signaling events inside the neuron that may result in the strengthening of existing connections between neurons, the growth of new connections, and the survival of the neuron itself. The researchers suggest that this may potentially be accompanied by an increase in conditioned avoidance reactions, suggesting that N-Acetyl Semax may affect cognitive brain functions by modulating the BDNF/trkB system in the hippocampus.

In addition to BDNF, N-Acetyl Semax may potentially affect another neurotrophic factor called NGF – nerve growth factor. Researchers suggest that N-acetyl Semax may result in the activation of the expression of the NGF and BDNG genes in the hippocampus, frontal cortex, and retina, with multidirectional action.^[6] In particular, the expression of NGF and BDNF genes may first increase in the frontal cortex initially, while later, there may be an increase in the hippocampus and retina area.

N-Acetyl Semax and Cerebral Functioning

One study used resting-state fMRI to examine the potential of N-Acetyl Semax on the central nervous system’s default mode network (DMN).^[7] The use of fMRI (functional magnetic resonance imaging) is based on the registration of shifts in the blood oxygenation level-dependent parameters (BOLD signal) in nerve tissue. The study commented that soon after N-Acetyl Semax instillation, the volume of the DMN network’s frontal subcomponent appeared significantly increased. The study also suggested the potential topographic locus of the actions of N-Acetyl Semax in the frontal compartments. The researchers noted that “The increase in the DMN frontal subcomponent in the main group was presented by a large cluster including the paracingular gyrus, frontal cingular cortex, and frontal pole.” This increase in spatial volumes of DMN subcomponents under the influence of N-Acetyl Semax may be due to the involvement of a greater number of neuronal populations in the network due to the synchronization of activity.

Another trial investigated the potential of N-Acetyl Semax on higher cerebral function and electroencephalography (EEG) patterns during cognitive activity.^[8] The study commented that Semax had a favorable impact on attention and short-term memory performance. EEG analysis suggested that Semax decreased delta rhythm and increased alpha and beta rhythms, indicating its anti-amnesic and nootropic potential.

N-Acetyl Semax and Gastric Mucosa

Some experiments suggest that N-acetyl Semax may also exert actions outside nervous tissues. Some studies suggest that the peptide may accelerate the clarification of ulcers from necrotic tissues and activate the process of cicatrization and epithelization.^[9] Other experiments suggest that this protective potential may be due to N-Acetyl Semax preventing the action of negative factors that would otherwise disrupt and reduce the normal blood flow to the gastric mucosa and result in ulcerogenesis.^[10]

Conclusion

In conclusion, N-Acetyl Semax is a synthetic peptide based on the structure of the naturally occurring ACTH and is additionally acetylated to increase its stability possibly. 

The peptide may potentially increase levels of neurotrophic factors in the brain, such as BDNF and NGF, which are considered important for the growth, survival, and maintenance of neurons. Upregulation of BDNF levels may have neuroprotective potential and act favorably on higher cerebral functions. 

Furthermore, N-Acetyl Semax potentially exerts actions outside nervous tissues, such as accelerating the clarification of ulcers from necrotic tissues and activating the cicatrization and epithelization in gastric mucosa.

However, further studies are needed to confirm these potential actions of N-Acetyl Semax.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

References

1. Magrì, A., Tabbì, G., Giuffrida, A., Pappalardo, G., Satriano, C., Naletova, I., Nicoletti, V. G., & Attanasio, F. (2016). Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. Journal of inorganic biochemistry, 164, 59–69. https://doi.org/10.1016/j.jinorgbio.2016.08.013
2. Kurysheva, N. I., Shpak, A. A., Ioĭleva, E. E., Galanter, L. I., Nagornova, N. D., Shubina, N. I.u, & Shlyshalova, N. N. (2001). “Semaks” v lechenii glaukomatoznoĭ opticheskoĭ neĭropatii u bol’nykh s normalizovannym oftal’motonusom [Semax in the treatment of glaucomatous optic neuropathy in patients with normalized ophthalmic tone]. Vestnik oftalmologii, 117(4), 5–8.
3. Gusev, E. I., Martynov, M. Y., Kostenko, E. V., Petrova, L. V., & Bobyreva, S. N. (2018). Éffektivnost’ semaksa pri lechenii bol’nykh na raznykh stadiiakh ishemicheskogo insul’ta [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 118(3. Vyp. 2), 61–68. https://doi.org/10.17116/jnevro20181183261-68
4. Dolotov, O. V., Karpenko, E. A., Seredenina, T. S., Inozemtseva, L. S., Levitskaya, N. G., Zolotarev, Y. A., Kamensky, A. A., Grivennikov, I. A., Engele, J., & Myasoedov, N. F. (2006). Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. Journal of neurochemistry, 97 Suppl 1, 82–86. https://doi.org/10.1111/j.1471-4159.2006.03658.x
5. Dolotov, O. V., Karpenko, E. A., Inozemtseva, L. S., Seredenina, T. S., Levitskaya, N. G., Rozyczka, J., Dubynina, E. V., Novosadova, E. V., Andreeva, L. A., Alfeeva, L. Y., Kamensky, A. A., Grivennikov, I. A., Myasoedov, N. F., & Engele, J. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain research, 1117(1), 54–60. https://doi.org/10.1016/j.brainres.2006.07.108
6. Shadrina, M., Kolomin, T., Agapova, T., Agniullin, Y., Shram, S., Slominsky, P., Lymborska, S., & Myasoedov, N. (2010). Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action. Journal of molecular neuroscience : MN, 41(1), 30–35. https://doi.org/10.1007/s12031-009-9270-z
7. Lebedeva, I. S., Panikratova, Y. R., Sokolov, O. Y., Kupriyanov, D. A., Rumshiskaya, A. D., Kost, N. V., & Myasoedov, N. F. (2018). Effects of Semax on the Default Mode Network of the Brain. Bulletin of experimental biology and medicine, 165(5), 653–656. https://doi.org/10.1007/s10517-018-4234-3
8. Kaplan, A. Y. A., Kochetova, A. G., Nezavibathko, V. N., Rjasina, T. V., & Ashmarin, I. P. (1996). Synthetic acth analogue semax displays nootropic‐like activity in humans. Neuroscience Research Communications, 19(2), 115-123.
9. Zhuĭkova, S. E., Badmaeva, K. E., Samonina, G. E., & Plesskaia, L. G. (2003). Semaks i nekotorye gliprolinovye peptidy uskoriaiut zazhivlenie atsetatnykh iazv u krys [Semax and some glyproline peptides accelerate the healing of acetic ulcers in rats]. Eksperimental’naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology, (4), 88–117.
10. Zhuikova, S. E., Sergeev, V. I., Samonina, G. E., & Myasoedov, N. F. (2002). Possible mechanism underlying the effect of Semax on the formation of indomethacin-induced ulcers in rats. Bulletin of experimental biology and medicine, 133(6), 577–579. https://doi.org/10.1023/a:1020285909696

This peptide appears to be naturally produced in the hypothalamus, where it is also known as gonadotropin-releasing hormone (GnRG), and may be rapidly degraded by enzymes called proteases. Gonadorelin appears to be a ligand for the receptors called gonadotropin-releasing hormone receptors (GnRH receptors), located on the surface of cells in the anterior pituitary gland.^[1] These receptors are members of the G protein-coupled receptor (GPCR) family, which scientists characterize by their seven-transmembrane domain structure. 

Activation of GnRH receptors appears to trigger intracellular signaling pathways, including the cyclic adenosine monophosphate (cAMP) pathway and the phospholipase C (PLC) pathway. These signaling pathways appear to be major regulators of the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. Research indicates that these hormones may be pivotally involved in the maturation and release of eggs in the ovaries and testosterone production. 

Gonadorelin (GnRH) and Gonadotropins

Gonadorelin exhibits apparent potential to bind to GnRH receptors located on pituitary cells, which may trigger a signaling cascade resulting in the transcription modulation of genes within the target cell. GnRH receptors are Gq-protein coupled, and their activation may induce the formation of receptor clusters that become internalized into the cell. Researchers should note that the GnRH receptors’ relatively short intracellular carboxy-terminal tail may prevent rapid desensitization.^[2]

According to research, two potential modes of Gonadorelin action on gonadotropins are pulsatile and surge modes.^[3] Pulsatile mode refers to periodic action, with clear pulses of gonadorelin into the portal circulation, while it remains undetectable between pulses. In female species, the surge mode of gonadorelin appears to occur during the preovulatory phase, where it may continuously present in the portal circulation.

Furthermore, researchers suggest that Gonadorelin may have different stimulatory actions on LH and FSH secretion, with FSH secretion being more irregular due to differences in storage, response times, and other factors. Pulsatile secretion of LH appears to be more strongly associated with Gonadorelin, while FSH has a constitutive secretion. The frequency of Gonadorelin pulses may selectively regulate gene transcription, with rapid pulses promoting LH formation and slow pulses promoting FSH formation.^[4]

Moreover, scientists hypothesize that after apparent initial stimulation of FSH and LH, continuous exposure to Gonadorelin either downregulates its receptors or its signaling pathway in pituitary cells.^[5] This hypothesis is based on observations that when the receptors appear to be exposed to a continuous action by gonadorelin, the “GnRH agonist (…) can actually act as an inhibitory agonist, thus reducing gonadotropin secretion.”

Gonadorelin (GnRH) and The Estrous Cycle

Scientists suggest two potential models of Gonadorelin’s action on the estrous cycle: the deterministic and permissive models. The deterministic model suggests that increasing Gonadorelin secretion may induce ovulation. In contrast, the permissive model suggests that the preovulatory LH surge may result from increased pituitary sensitivity to Gonadorelin without necessarily an increase in gonadorelin secretion. Studies in rodents, rabbits, and sheep support the deterministic model, while studies in primates suggest the permissive model may be correct.^[6]

Regardless, research experiments across various animal models point to Gonadorelin’s likely role in the estrous cycle. One animal study aimed to evaluate its potential to induce ovulation in female cats.^[7] The study divided 27 female cats into a Gonadorelin group and a placebo group that received saline solution. Results suggested that 84% of the female cats which received Gonadorelin had ovulated, while only 37% of the placebo group had ovulated. 

One trial also aimed to assess the action of Gonadorelin on premature ovarian failure (POF) compared to a placebo for four weeks. The scientists posited that apparently, 20% of the agonist group ovulated, compared to none in the placebo group.^[8] They also commented that “Follicular growth was seen in five [..] of the agonist group and in four [..] of the placebo group.” Premature ovarian failure is a condition in which the ovaries stop functioning too early. This may result in infertility, amenorrhea, dyspareunia, hyperhidrosis, etc. The cause of premature ovarian failure is not always known, but genetic factors, autoimmune disorders, and certain infections may induce it. 

Gonadorelin (GnRH) and The Nervous System

Research indicates that Gonadorelin and GnRH receptors are present in different brain areas and may induce various actions. Studies hypothesize that Gonadorelin may increase the expression of cytoskeletal proteins and promote neuronal outgrowth in the cerebral cortex since GnRH receptors appear abundant amongst the neurons in these areas of the brain.^[9]

Gonadorelin may also alter neural circuitry underlying visual working memory, but the mechanism of action is unclear. In the cerebellum, Gonadorelin and GnRH receptors have been reportedly detected in Purkinje cells and are suggested to potentially affect both glutamate and GABA content. In turn, this suggests a potential role in regulating their interactions. 

Finally, high densities of GnRH receptors have been detected in the CA1-CA3 regions of the hippocampus, and activation of these receptors has been proposed to affect sexual behavior regulation in mammals, as well as an increase in intrinsic neuronal excitability and synaptic transmission.

Conclusion

Gonadorelin is a decapeptide that may play a role in the hypothalamic-pituitary-gonadal axis. Its potential to bind to gonadotropin-releasing hormone receptors may trigger intracellular signaling pathways that regulate the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. 

Gonadorelin also appears to play an essential role in the estrous cycle and especially its ovulatory phase, which may be potentially due to a peak in its levels or a peak in a change in the sensitivity of the gonadotropin-releasing hormone receptors. Moreover, the presence of Gonadorelin and GnRH receptors in various brain regions suggests that it may have neuromodulatory action beyond its well-known role in gonadotropin release and the estrous cycle.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

References

1. Perrett, R. M., & McArdle, C. A. (2013). Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network. Frontiers in endocrinology, 4, 180. https://doi.org/10.3389/fendo.2013.00180
2. Casteel CO, Singh G. Physiology, Gonadotropin-Releasing Hormone. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558992/
3. Maeda, K., Ohkura, S., Uenoyama, Y., Wakabayashi, Y., Oka, Y., Tsukamura, H., & Okamura, H. (2010). Neurobiological mechanisms underlying GnRH pulse generation by the hypothalamus. Brain research, 1364, 103–115. https://doi.org/10.1016/j.brainres.2010.10.026
4. Marques P, Skorupskaite K, Rozario KS, et al. Physiology of GnRH and Gonadotropin Secretion. [Updated 2022 Jan 5]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279070/
5. Jones, R. E., & Lopez, K. H. (2013). Human reproductive biology. Academic Press.
6. Karsch, F. J., Bowen, J. M., Caraty, A., Evans, N. P., & Moenter, S. M. (1997). Gonadotropin-releasing hormone requirements for ovulation. Biology of reproduction, 56(2), 303–309. https://doi.org/10.1095/biolreprod56.2.303
7. Ferré-Dolcet, L., Frumento, P., Abramo, F., & Romagnoli, S. (2021). Disappearance of signs of heat and induction of ovulation in oestrous queens with gonadorelin: a clinical study. Journal of feline medicine and surgery, 23(4), 344–350. https://doi.org/10.1177/1098612X20951284
8. van Kasteren, Y. M., Hoek, A., & Schoemaker, J. (1995). Ovulation induction in premature ovarian failure: a placebo-controlled randomized trial combining pituitary suppression with gonadotropin stimulation. Fertility and sterility, 64(2), 273–278. https://doi.org/10.1016/s0015-0282(16)57722-x
9. Martínez-Moreno, C. G., Calderón-Vallejo, D., Harvey, S., Arámburo, C., & Quintanar, J. L. (2018). Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?. International journal of molecular sciences, 19(2), 375. https://doi.org/10.3390/ijms19020375

Scientists consider TREK-1 to be widely expressed in the central nervous system,  playing a possible role in pain perception, mood regulation, and neuroprotection. PE-22-28 has exhibited potential binding activity to the extracellular domain of TREK-1, thereby inhibiting the channel’s activity. Further research is needed to fully understand the mechanisms of action and potential research applications of PE-22-28 peptide. PE 22–28 has also been used as the core peptide to design other analogs with different N- and C-terminal end modifications. 

PE-22-28 Peptide and TREK-1 Inhibition

The primary potential  mechanism of action of PE-22–28 peptide is considered by researchers to be exerted via blocking the TREK-1 channels in the central nervous system. According to Djillani et al., PE-22–28 is “the shortest, most efficient sequence capable of blocking the TREK-1 channel with higher potency” than spadin.^[2] TREK-1 is generally the most studied background two-pore domain potassium channel. Its main role is considered to be controling cell excitability and maintaining the membrane potential below the threshold of depolarization.^[3] TREK-1 may also be multi-regulated by a variety of physical and chemical stimuli. TREK-1 has also been reported in the heart and several other organs, but inhibition of these channels has unknown impact.^[4]

By blocking TREK-1, murine studies suggest that PE-22–28 may significantly decrease immobility time in the forced swim test (FST) compared to control mice that received saline.^[1] The FST is a common test used to measure depressive behavior in rodents, where the mice are placed in a water tank, and their mobility is monitored. In addition, the study also evaluated the potential of PE-22–28 on the learned helplessness test (LHT), another test with similar indications as FST. The LHT measures the time it takes for mice to escape from an aversive stimulus. The study commented that the sub-chronic presentation of PE-22–28 appears to significantly reduce the escape latencies in the LHT.

Furthermore, the trial evaluated the potential of PE-22-28 on a mice model of long-term corticosterone presentation.^[1] Corticosterone is a hormone that is involved in the body’s response to stress, and chronic exposure to high levels of corticosterone has been associated with depressive behavior in rodents. The results of this study suggested that PE-22–28 peptide may result in decreasing immobility time in the FST. It may also reduce the latency to eat in the novelty-suppressed feeding (NSF) test, which measures an animal’s willingness to eat in a stressful environment.

PE-22-28 Peptide and Serotonin Transmission

Researchers posit that PE-22–28 may inhibit TREK-1, possibly leading to the excitation of the dorsal raphé nucleus and the firing of serotonin transmission.^[5] The researchers suggest that “if a viral vector that leads to the secretion of PE 22-28 is [presented to] the dorsal raphé nucleus, the peptide will block the channel and thereby activate the serotonergic neurons, resulting in the facilitation of serotonergic transmission, as SSRIs do.”

Studies suggest that PE-22–28 peptide may act as a blocker of the TREK-1 channel, similar to spadin, and Maati et al. investigated these actions in relation to the connectivity between the medial prefrontal cortex (mPFC) and dorsal raphé serotonergic neurons.^[6] The study commented that spadin might increase the firing rate of serotonin neurons and that the action of spadin and 5-HT4 agonists appeared additive and independent of each other. However, adding a mGluR2/3 antagonist reportedly blocked the action of spadin, suggesting that spadin likely depends on mPFC TREK-1 channels coupled to mGluR2/3 receptors. Therefore, the researchers further suggested that PE-22-28 may also interact with the mGluR2/3 receptors, similar to spadin, to fire up the serotonin neurons. 

The mGluR2/3 is a metabotropic glutamate receptor found in the central nervous system. They are G protein-coupled receptors that are considered to be activated by the neurotransmitter glutamate. There are two subtypes of mGluR2/3 receptors: mGluR2 and mGluR3, and they are both involved in regulating neurotransmitter release.^[7] Activation of mGluR2/3 receptors appears to inhibit the release of glutamate and other neurotransmitters, such as GABA and dopamine. This mechanism may help to regulate synaptic transmission and maintain the balance of excitatory and inhibitory neurotransmission in the brain. The study also suggested that the combination of 5-HT activators should be cautiously approached.^[6]

PE-22-28 Peptide and Neuroplasticity

One in vitro trial suggested that inhibiting TREK-1 may increase neuronal membrane potential and activate both MAPK and PI3K signaling pathways in a time- and concentration-dependent manner.^[8] The latter pathway has been linked to the supposed protective action of spadin against apoptosis. Inhibiting TREK-1 also appeared to enhance mRNA expression and protein levels of two markers of synaptogenesis, PSD-95, and synapsin. Inhibiting TREK-1 may increase the proportion of mature spines in cortical neurons, suggesting increased neuroplasticity. Inhibiting TREK-1 appeared in other experimental models to increase mRNA expression and protein levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, suggesting a neuroplasticity potential.^[8]

In one murine model, PE-22-28 was presented for 4 days, and on the 5th day, the brains of the rats were analyzed.^[1] The results suggested that PE-22-28 significantly increased the number of bromodeoxyuridine (BrdU) positive cells in the hippocampus compared with saline mice, suggesting that PE-22-28 may induce hippocampal neurogenesis similar to spadin. BrdU is a thymidine analog that incorporates the DNA of dividing cells during the S-phase of the cell cycle.

Conclusion

PE-22-28 is a synthetic peptide analogous to spadin, a protein naturally produced in the central nervous system and considered by researchers to possibly inhibit the action of TREK-1. As a result, the peptide appears to upregulate serotonin production, possibly improving neuroplasticity and reducing depressive behavior in animal models. Nevertheless, more research is needed to evaluate its potential actions.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

References

1. Djillani, A., Pietri, M., Moreno, S., Heurteaux, C., Mazella, J., & Borsotto, M. (2017). Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Frontiers in pharmacology, 8, 643. https://doi.org/10.3389/fphar.2017.00643
2. Djillani, A., Pietri, M., Mazella, J., Heurteaux, C., & Borsotto, M. (2019). Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin. Pharmacology & therapeutics, 194, 185–198. https://doi.org/10.1016/j.pharmthera.2018.10.003
3. Djillani, A., Mazella, J., Heurteaux, C., & Borsotto, M. (2019). Role of TREK-1 in Health and Disease, Focus on the Central Nervous System. Frontiers in pharmacology, 10, 379. https://doi.org/10.3389/fphar.2019.00379
4. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 1996 Dec 16;15(24):6854-62. PMID: 9003761; PMCID: PMC452511.
5. Okada, M., & Ortiz, E. (2022). Viral vector-mediated expressions of venom peptides as novel gene therapy for anxiety and depression. Medical Hypotheses, 166, 110910.
6. Moha ou Maati, H., Bourcier-Lucas, C., Veyssiere, J., Kanzari, A., Heurteaux, C., Borsotto, M., Haddjeri, N., & Lucas, G. (2016). The peptidic antidepressant spadin interacts with prefrontal 5-HT(4) and mGluR(2) receptors in the control of serotonergic function. Brain structure & function, 221(1), 21–37. https://doi.org/10.1007/s00429-014-0890-x
7. Jin LE, Wang M, Galvin VC, Lightbourne TC, Conn PJ, Arnsten AFT, Paspalas CD. mGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks. Cereb Cortex. 2018 Mar 1;28(3):974-987. doi: 10.1093/cercor/bhx005. PMID: 28108498; PMCID: PMC5974790.
8. Devader, C., Khayachi, A., Veyssière, J., Moha Ou Maati, H., Roulot, M., Moreno, S., Borsotto, M., Martin, S., Heurteaux, C., & Mazella, J. (2015). In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin. British journal of pharmacology, 172(10), 2604–2617. https://doi.org/10.1111/bph.13083

Since its initial discovery, Vilon has been the subject of numerous studies in Russia and other countries. Its potential action may include interacting with genes, cell proliferation, immune system functioning, coagulation, cell aging, organ function, and even cancer cells.

Vilon is arguably the shortest peptide to have any biological activity and is made of two amino acids, lysine, and glutamate. This has led to the peptide being recognized as Lysylglutamic acid or Lysylglutamate. Vilon has a chemical formula of C11H21N3O5 and a molecular weight of 275.30 g/mol. The amino acid L-lysine is a positively charged amino acid, while L-glutamate is a negatively charged amino acid. This gives Vilon (Lysylglutamate) an overall neutral charge.

Overall, the structure of Vilon is relatively simple compared to larger peptides and proteins. Still, its unique composition and chemical properties make it an interesting molecule for further study and potential development.

Research Studies on the Vilon Peptide

Vilon Peptide and Cell Proliferation, Gene Expression

Studies suggest that Vilon may affect gene expression and, more specifically, programmed cell death (apoptosis). One laboratory experiment reported that the peptide reduced the apoptotic death of spleen lymphocytes in rats caused by irradiation.^[1]

Another study examined the potential of Vilon on cell proliferation in spleen organotypic tissue cultures of rats of different ages (3 days, 3 weeks, and 2 years old). The results suggested that Vilon might stimulate cell proliferation in both young and old rats.^[2]

The peptide may achieve this effect by interacting directly with certain genes. Experiments reveal that Vilon may have the ability to modify the chromatin structure of lymphocytes in elderly research models.^[3] This may lead to the release and activation of genes that are otherwise repressed due to aging.

Vilon Peptide and Cell Aging

Animal studies reported that exposure to Vilon (Lys-Glu) in female CBA mice from the 6th month of life might enact physical activity, endurance, and prolonged lifespan while preventing spontaneous neoplasms.^[4] According to the study, the introduction of Vilon did not appear to affect the estrous function or free radical processes. The long-term exposure of Vilon did not appear to cause any negative impact on animal development either, indicating that it may be efficacious for geroprotection.

Several studies also report that the peptide may activate regeneration mechanisms in explanted cells in young and aged rats.^[5][6] The peptide was reportedly effective, even in small concentrations. The researchers noted that “the stronger effect on the explants taken from the old rats suggests that Vilon is a candidate for geriatric research and practice.”

Another study suggested that low-concentration ionizing radiation appeared to cause accelerated cell aging in the thymus and spleen of rats; 7 however, exposure to Vilon appeared to partially inhibit this process and furthermore provided anti-cell aging characteristics.

Vilon Peptide and the Immune System

Experiments in murine models of immunosuppression report that Vilon may have immunomodulating action. One animal study examined the effect of Vilon exposure in rats exposed to mercury and gamma radiation, which are known to suppress the immune system. The exposure caused lymphopenia and DNA damage, but the Vilon peptide appeared to normalize the lymphocyte count and reduce the morbidity of rats over a period of 15 months after exposure.^[8]

In another study, Vilon was suggested by researchers to increase the expression of lymphocyte differentiation marker CD5 in thymic cells. It appeared to induce T-cells precursor differentiation towards CD4+ T-helpers.^[9] CD4+ T-helper cells are a type of white blood cell that plays a crucial role in the immune response by activating and coordinating the activity of other immune cells. Vilon was suggested to stimulate the expression of argyrophilic proteins in nucleolar organizer regions of thymocytes and epithelial cells and promote thymocyte transformation into proliferating blast cells.^[10]

Vilon Peptide and Coagulation

The possible action of the peptide on coagulation is one of the less developed hypotheses put forth by researchers. One study reported that Vilon appeared to significantly reduce or eliminate accelerated blood coagulability, decrease levels of natural anti-coagulants, and increase fibrinogen and fibrin complexes in research models of type 1 diabetes.^[11] This finding was reported despite the action appearing to be less pronounced in elderly models of severe forms of the disease.

Another trial in aged research models of type 1 diabetes reported that Vilon appeared to increase natural anticoagulant content, stimulate fibrinolysis, and reduce insulin supplementation.^[12] Vilon purportedly did so by stabilizing the immune system by normalizing active T-lymphocytes, B-lymphocytes, and IgA while reducing T-helpers’ content, T-dependent, and non-T-dependent NK cells. The researchers also reported that “in most cases, Vilon reduced the [concentration] of insulin necessary for the stabilization of carbohydrate metabolism.”

Vilon Peptide and Cancer Cells

Vilon was developed as an immunomodulator and has also been studied in stage III rectal and colon cancer.^[13] Researchers suggested it may potentially improve the 2-year survival rate, mitigate post-operative and remote complications, recurrences, and tumor dissemination. However, it is important to note that these findings are based on preliminary results and require further investigation.

According to one murine model of bladder cancer, exposure to Vilon appeared to reduce the incidence of preneoplastic and early neoplastic changes in urinary bladder mucosa and significantly inhibited carcinogenesis.^[14] The incidence of urinary bladder tumors was also reportedly lower in Vilon-exposed animals than controls. However, some studies report conflicting results. One animal experiment reports that Vilon appeared to increase the incidence of mammary cancer and shorten the time for tumor development in female transgenic mice.^[15]

Conclusion

Vilon is a synthetically developed peptide comprised of two amino acids with strong immunomodulatory potential. It has been studied extensively since its development and has been suggested to host numerous potential actions. While much is still unknown about the mechanisms of action and the full breadth of potential downstream impacts of Vilon, its development represents an important milestone in the search for new tools that interact with immunity, gene expression, and cell aging.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

References

1. Khavinson VK, Kvetnoii IM. Peptide bioregulators inhibit apoptosis. Bull Exp Biol Med. 2000;130(12):1175-1176.
2. Bykov NM, Chalisova NI, Zeziulin PN. Retsiproknye sootnosheniia proliferativenoĭ aktivnosti v tsentral’noĭ i perifericheskoĭ zonakh organotipicheskoĭ kul’tury selezenki pri deĭstvii vilona u krys raznogo vozrasta [Reciprocal relation of proliferative activity in central and peripheral zones of splenic organ culture exposed to vilon in rats of various ages]. Adv Gerontol. 2003;11:104-108.
3. Lezhava T, Monaselidze J, Kadotani T, Dvalishvili N, Buadze T. Anti-aging peptide bioregulators induce reactivation of chromatin. Georgian Med News. 2006;(133):111-115.
4. Khavinson VK, Anisimov VN, Zavarzina NY, et al. Effect of vilon on biological age and lifespan in mice. Bull Exp Biol Med. 2000;130(7):687-690. doi:10.1007/BF02682106
5. Kniaz’kin IV, Iuzhakov VV, Chalisova NI, Grigor’ev EI. Funktsional’naia morfologiia organotipicheskoĭ kul’tury selezenkoi krys razlichnogo vozrasta pri deĭstvii vilona [Functional morphology of organotypic culture of spleens from rats of various ages exposed to vilon]. Adv Gerontol. 2002;9:110-115.
6. Bykov NM, Chalisova NI. Osobennosti deĭstviia ul’tramalykh doz vilona v organotipicheskoĭ kul’ture selezenki krys raznogo vozrasta [Characteristics of effect of ultralow doses of vilon in organotypic culture of spleens from rats of various ages]. Adv Gerontol. 2002;10:85-87.
7. Kniaz’kin IV, Poliakova VO. Deĭstvie vilona na timus i selezenku v radiatsionnoĭ modeli prezhdevremennogo stareniia [The effect of vilon on the thymus and spleen in a radiation model of premature aging]. Adv Gerontol. 2002;9:105-109.
8. Ivanov SD, Khavinson VKh, Malinin VV, et al. Adv Gerontol. 2005;16:88-91.
9. Sevostianova NN, Linkova NS, Polyakova VO, et al. Immunomodulating effects of Vilon and its analogue in the culture of human and animal thymus cells. Bull Exp Biol Med. 2013;154(4):562-565. doi:10.1007/s10517-013-2000-0
10. Raikhlin NT, Bukaeva IA, Smirnova EA, et al. Expression of argyrophilic proteins in the nucleolar organizer regions of human thymocytes and thymic epitheliocytes under conditions of coculturing with vilon and epithalon peptides. Bull Exp Biol Med. 2004;137(6):588-591. doi:10.1023/b:bebm.0000042720.40439.16
11. Kuznik BI, Kolesnichenko LR, Kliuchereva NN, Pinelis IuI, Ryzhak GA, Khamaeva TsB. Adv Gerontol. 2006;19:107-115.
12. Kuznik BI, Isakova NV, Kliuchereva NN, Maleeva NV, Pinelis IS. Adv Gerontol. 2007;20(2):106-115.
13. Ias’kevich LS, Krutilina NI, Kostetskaia TV, Ryzhak GA, Khavinson VKh. Adv Gerontol. 2005;16:97-100.
14. Pliss GB, Mel’nikov AS, Malinin VV, Khavinson VK. Inhibitory effect of peptide vilon on the development of induced rat urinary bladder tumors in rats. Bull Exp Biol Med. 2001;131(6):558-560. doi:10.1023/a:1012354603132
15. Anisimov VN, Khavinson VK, Provinciali M, et al. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2002;101(1):7-10. doi:10.1002/ijc.10570

Liraglutide peptide was first developed in the 1990s, with the intention to improve blood sugar control in cases of type 2 diabetes. The development of Liraglutide was based on the discovery of the hormone glucagon-like peptide-1 (GLP-1), which is involved in regulating blood sugar levels. It has been widely researched since its development, with some studies outlined below.

Liraglutide Peptide and Body Composition

Liraglutide peptide may have significant potential in regulation of weight and lean mass. One study focused on obese and overweight research models, with findings exhibiting a loss of at least 5% of initial weight.^[1] The models were randomly exposed either to Liraglutide peptide or a placebo for 56 weeks, which appeared to lead to additional weight loss on average for the study period. Liraglutide peptide also appeared to produce small improvements in some cardiovascular risk factors. The scientists reported that “From randomization to week 56, weight decreased an additional mean 6.2%  […] with liraglutide and 0.2% […] with placebo.” Another 56-week-long study reported similar results, with an average of 5-6% of observed weight loss in most models under observation.^[2]

Researchers also suggested that Liraglutide peptide and prolonged physical activity may lead to a 2-fold rate of weight loss compared controls subjected to physical activity alone.^[3] One of the longest studies to investigate the action of Liraglutide peptide in weight was a 20-week randomized, double-blind, placebo-controlled study with a 2-year extension involving 564 overweight research models.^[4] Receiving either Liraglutide peptide, a placebo, or an open-label weight loss compound in addition to carefully monitored nutritional intake and physical output. The study’s results suggested that Liraglutide peptide-exposed models lost more weight than those on a placebo or compound. Moreover, the research models exposed to Liraglutide also appeared to experience improvements in metabolic syndrome and blood pressure.

Liraglutide and the Endocrine System

Liraglutide peptide has some potential to act as an incretin in the endocrine system, specifically in the pancreas, which enhances insulin secretion. The peptide was developed to mimic the action of the incretin hormone GLP-1, which stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner.^[5] The effect appears to depend on the serum glucose levels, diminishing if the glucose is low and thereby preventing the occurrence of hypoglycemia.

When Liraglutide peptide was delivered to research models of type 2 diabetes, studies suggest it may enhance the incretin effect by increasing GLP-1 levels in the bloodstream. This leads to increased insulin secretion and decreased glucagon secretion, resulting in improved blood sugar control. These studies reported apparently significant improvements in various parameters related to blood sugar control in model of type 2 diabetes.^[6] These included improved levels of glycated hemoglobin, body mass index (BMI), cardiovascular parameters, etc., all within the 3-6 months of the study. The scientists reported that the “meaningful difference in weight, body mass index, glycated hemoglobin (HbA1C), systolic blood pressure, and diastolic blood pressure from baseline to follow-up was -5.36 kg, -2.14 kg/m2, -1.76%, -12.38 mmHg, and 5.55 mmHg, respectively.” In addition, experiments observed that Liraglutide might also exhibit a protective action on the function of the pancreas in type 2 diabetes cases and preserve the function of the beta cells, which normally produce insulin.^[7]

Liraglutide Peptide and the Digestive System

Liraglutide peptide may slow down the emptying of food from the stomach into the small intestine, leading to prolonged satiety and reduced appetite. Research studies suggest that 1-h gastric emptying was, on average, 23% lower in studies than controls, although that performance appeared to be concentration-dependent.^[8] Scientists reported that the speed of gastric emptying eventually returned to normal after 4 hours.

Liraglutide Peptide and the Nervous System

Apart from slowing down gastric emptying, Liraglutide peptide has also been suggested by researchers to suppress appetite by directly affecting the brain via reduced hunger hormone signaling. This potential may be due to the peptide’s hypothetical interaction with GLP-1 receptors in the brain, whose activation may lead to reduced appetite.^[9] Liraglutide peptide has suggested promise in neuroprotection, as reported in murine models of Parkinson’s Disease (PD),^[10] with scientists suggesting that the peptide might reduce neuroinflammation and reduce neuron loss.

PD is a neurodegenerative disorder that affects the nervous system, particularly the dopaminergic neurons in the brain. While the exact cause of PD is unknown, some data suggests that an autoimmune reaction that destroys these neurons may contribute to the development of the disease.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.
 

References

1. Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study [published correction appears in Int J Obes (Lond). 2013 Nov;37(11):1514] [published correction appears in Int J Obes (Lond). 2015 Jan;39(1):187]. Int J Obes (Lond). 2013;37(11):1443-1451. doi:10.1038/ijo.2013.120
2. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial [published correction appears in JAMA. 2016 Jan 5;315(1):90]. JAMA. 2015;314(7):687-699. doi:10.1001/jama.2015.9676
3. Lundgren JR, Janus C, Jensen SBK, et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021;384(18):1719-1730. doi:10.1056/NEJMoa2028198
4. Astrup A, Carraro R, Finer N, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide [published correction appears in Int J Obes (Lond). 2012 Jun;36(6):890] [published correction appears in Int J Obes (Lond). 2013 Feb;37(2):322]. Int J Obes (Lond). 2012;36(6):843-854. doi:10.1038/ijo.2011.158
5. Neumiller JJ, Campbell RK. Liraglutide: a once-daily incretin mimetic for the treatment of type 2 diabetes mellitus. Ann Pharmacother. 2009;43(9):1433-1444. doi:10.1345/aph.1M134
6. Zameer R, Kamin M, Raja U, et al. Effectiveness, Safety, and Patient Satisfaction of Liraglutide in Type 2 Diabetic Patients. Cureus. 2020;12(8):e9937. Published 2020 Aug 22. doi:10.7759/cureus.9937
7. Kapodistria K, Tsilibary EP, Kotsopoulou E, Moustardas P, Kitsiou P. Liraglutide, a human glucagon-like peptide-1 analogue, stimulates AKT-dependent survival signalling and inhibits pancreatic β-cell apoptosis. J Cell Mol Med. 2018;22(6):2970-2980. doi:10.1111/jcmm.13259
8. van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond). 2014;38(6):784-793. doi:10.1038/ijo.2013.162
9. Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014;15(3):181-187. doi:10.1007/s11154-014-9289-5
10. Cao B, Zhang Y, Chen J, Wu P, Dong Y, Wang Y. Neuroprotective effects of liraglutide against inflammation through the AMPK/NF-κB pathway in a mouse model of Parkinson’s disease. Metab Brain Dis. 2022;37(2):451-462. doi:10.1007/s11011-021-00879-1