Selank

Selank is a peptide chain composed of two fragments: one is Tuftsin at the N-terminal end and the other is a Pro-Gly-Pro (PGP) tripeptide at the C-terminal end of the molecule. The inclusion of a Pro-Gly-Pro (PGP) sequence in the Selank peptide could improve its potential to penetrate various biological barriers, including the blood-brain barrier (BBB). The BBB is a highly selective and semipermeable membrane that delineates circulating blood from brain tissues and extracellular fluid within the central nervous system. It is considered to play a fundamental role in controlling the entry of molecules. The integration of the PGP sequence could modify the hydrophilicity or lipophilicity of the peptide, which could increase its compatibility with the lipid-rich environment of the BBB. Furthermore, the PGP motif could interact with certain transport systems or receptors on the BBB membrane, potentially facilitating receptor-mediated endocytosis or active transport. These mechanisms may allow Selank to bypass tight junctions that typically impede the transit of larger molecules across the BBB. Additionally, the presence of the PGP sequence could alter the tertiary structure of Selank, making it potentially more susceptible to crossing the BBB. This alteration could arise from changes in the spatial configuration of the peptide, which can influence its interaction with cellular components of the BBB.(6)

Chemical Composition

• Molecular Formula: C33H57N11O9
• Molecular Weight: 751.88 g/mol
• Other Known Titles: TP-7, Selanc

There is a possibility that Selank may influence the expression of brain-derived neurotrophic factor (BDNF), considered a crucial protein in the brain that supports neuronal survival and growth.(1) Research indicates that Selank can notably increase BDNF mRNA levels in the hippocampus, an integral region of the brain involved in memory and emotional responses. Selank's potential to increase BDNF expression, particularly under conditions where stress and glucocorticoids suppress BDNF levels, suggests its relevance in research studies within the context of impaired neuroplasticity. The perceived role of this protein in synaptic function and neuronal adaptation underscores the importance of such investigations.

Selank may potentially influence serotonin signaling mechanisms. It is theorized that serotonin signaling plays a crucial role in managing mood and anxiety within the brain. Research using murine models where serotonin synthesis was inhibited has indicated that Selank might be able to alter serotonin levels in cases where the serotonergic system is impaired. Researchers have proposed that Selank can potentially increase serotonin metabolism in the brainstem, indicating its potential action on the serotonin system. More specifically, the peptide is believed to facilitate an increase in the metabolic processing of serotonin in brain regions considered essential for mood and anxiety regulation. Furthermore, the hypothesis that Selank may improve serotonin metabolism suggests a potential pathway by which Selank could improve issues stemming from decreased serotonin activity.

Studies have suggested that Selank may act on gamma-aminobutyric acid (GABA) receptors. GABA is considered an inhibitory neurotransmitter within this context, playing a role in decreasing neuronal excitability, fostering relaxation, and mitigating observations of anxiety, as seen in animal research models. In a study,(7) the expression of 84 genes involved in neurotransmission was studied in murine models. Experimental murine models were exposed to Selank or GABA, and gene expression was studied after one and three hours using a PCR method. All gene expressions studied for Selank and GABA appeared positively correlated. Results suggested that Selank had the potential to induce various alterations in the neurotransmission process, suggesting by proxy that Selank may exert a possible action through modulation of the GABAergic system. Furthermore, literature indicates that Selank's influence might not be limited to mere direct actions on transcriptional activity of genes associated with GABA receptors. It could also imply allosteric modulation of the GABAergic system. This is inferred from observed variations in gene expression after exposure to Selank compared to GABA, where it has been speculated that Selank distinctively affects the expression of specific genes. Such differential gene expression alludes to a more complex interaction of Selank with the GABAergic system, possibly diverging from direct receptor activation typically seen with GABA. It has also been proposed that Selank instigates lasting modifications within neurotransmitter systems, a characteristic that could explain its extended anxiolytic actions observed in experimental frameworks. These alterations suggest a broader and potentially long-term impact on neurotransmitter dynamics beyond potential receptor interaction, emphasizing Selank's complex potential in neural regulation.

Studies have been conducted to understand the potential of the Selank peptide on genome expression and its involvement in the inflammatory process. These studies(8) were conducted on male murine models weighing 250 grams. These murine models were separated into three groups: a control group, an experimental group with a single exposure to Selank, and an experimental group under routine exposure to Selank. After the study, RNA was isolated from the rat spleen and hippocampus and studied via the PCR method. Based on the results, researchers suggested that Selank might have the potential to impact gene expression, exhibited more definitively in the spleen and hippocampus. One of the gene expressions reported during the study was the change in CX3CR1, which was involved in the inflammatory process. This suggested that Selank could regulate the inflammatory process through the gene expression mechanism, primarily the alteration of CX3CR1.

In a clinical study,(9) 62 research models of Generalized Anxiety Disorder (GAD) were examined. These models were divided into two groups: 48% were exposed to Selank, while 52% were exposed to a generic benzodiazepine compound. After the study, psychometric levels of all models were analyzed. Results suggested that Selank's impact appeared to be similar to that of the generic compound. Researchers also reported that enkephalin levels of tau leu-enkephalin were apparently reduced in the group exposed to Selank prior to the experiment, and the addition of Selank may have reversed this observation. It is hypothesized that Selank exerts suppressive actions on enzymes that break down enkephalins. Enkephalins, which are endogenous ligands for opioid receptors, have been implicated in the regulation of pain, mood, and stress responses. Therefore, potential inhibition of these degrading enzymes by Selank could result in increased levels of enkephalins, potentially increasing their physiological actions. This could lead to a notable elevation in concentrations of tau(1/2) leu-enkephalin during experiments involving anxiety models where Selank is evaluated.

This study(11) was conducted on murine models that were enrolled in a four-day "training" session to learn the conditioned avoidance response (CAR). CAR is a learned response to delay or prevent avoidance behavior. Exposure to Selank was initiated 15 minutes before the training session on all four days. Upon monitoring the behavior of the murine models, researchers suggested that the learning skills of the murine models appeared to improve with each exposure of the peptide, as the number of errors was reduced and the number of correct solutions increased. This potential impact could be mediated through multiple interconnected pathways, including the modulation of neuropeptide systems within the brain. These neuropeptides are considered critical as they are believed to play significant roles in various cognitive functions, potentially driving processes related to learning and memory. Furthermore, the Selank peptide could alter neuronal circuits involved in memory consolidation. This alteration may improve synaptic stability and efficiency in learning processes. Additionally, Selank could indirectly boost cognitive performance by mitigating anxiety-related factors that frequently impede learning efficiency. This suggests that Selank may influence emotional aspects of cognition, improving the general cognitive process. Moreover, Selank may promote neural plasticity or the ability of neurons to adapt, particularly in cognitive circuits that are not functioning optimally, thus potentially elevating their function. This improvement of neural adaptability may be vital for the maintenance and improvement of cognitive skills, suggesting that Selank could be a valuable compound for future investigations in neurocognitive fields.

This clinical study(12) was conducted on GAD research models with neurasthenia, with a control group and an experimental group exposed to the Selank peptide for 14 days. After the study, peripheral blood samples were collected and analyzed. Analytical results suggested a maximum elevation in IL-6 cytokine levels and changes in the ratio of Th1 and Th2 cytokines, all of which are believed to regulate the immune system.

In this study,(13) murine models were infused with 10% ethanol as their sole source of fluid for 24 weeks. Consequently, these murine models were experimentally induced with alcohol withdrawal symptoms once the ethanol drip was removed. The murine models were then exposed to Selank, to study its potential impact on withdrawal symptoms. After 48 hours, researchers reported that alcohol withdrawal symptoms appeared to have reduced, according to results from their social interaction and maze tests.

In this study,(14) Selank was presented to feline models. The main objective of this study was to examine the cardiovascular and respiratory potential of the peptide in this specific model. Upon exposure to the peptide, researchers reported that there appeared to be a 32% decrease in arterial pressure within 3 minutes following the presence of the peptide. Additionally, the peptide possibly induced a 24% increase in cerebral blood flow within the first 10 minutes, slowing declining to optimal levels. Selank was not reported to have induced any action on the respiratory system or heart rate.

In this study,(15) murine models were first exposed to a high-fat diet for 6 consecutive weeks until the weights of the murine models measured between 280g and 300g. Later, these murine models were divided into two groups, a control group given sodium chloride and an experimental group exposed to the Selank peptide. Additionally, a group of control murine models was used for this study, which were not presented with any of the agents, but were simply monitored for the purpose of the study. Upon analysis, researchers suggested that the Selank group exhibited apparently decreased levels of cholesterol and fat anywhere between 25% and 58%. Based on findings, Selank may also reduce specific forms such as low-density lipoprotein (LDL) cholesterol, very low-density lipoproteins (VLDL), and triglycerides. This indicates that Selank could play a direct or indirect role in influencing lipid metabolism mechanisms and could potentially show actions that reduce cholesterol (hypocholesterolemic) and lipid levels (hypolipidemic). Furthermore, the research noted discernible improvements in parameters related to hemostasis, including elevated total fibrinolytic activity and decreased platelet aggregation, which may suggest improvements in conditions favoring clot formation. Additionally, the study points to a possible modulatory action of Selank on glucose homeostasis, which implies maintaining stable blood glucose levels. The fat metabolism rate of the Selank group also reportedly improved and was finally measured at the same rate as the control models. Upon determination of the weight of the murine models, it was observed that the control group exhibited an average weight gain of 40g throughout the study, while the experimental group maintained the same weight throughout the study, with a gradual weight reduction following peptide presentation.