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Peptides for the Brain

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Peptides for the Brain | What to Know in 2023

The last decade has witnessed an explosion of research into the effects of peptides for brain and central nervous system. As a result of this research, science has come to understand that multiple peptides have a complex and nuanced effect on the brain under both physiological circumstances as well as pathological conditions. What is even more interesting is that the last 10 years have revealed that early research for brain peptides, in many cases, incorrectly identified the peptide’s major role. In other words, for a long time, science has not known what the major roles of specific peptides are in the brain. It is only recently that research has become sophisticated enough to the point that we are finally beginning to understand the most important roles of peptides for the brain.

 

Peptides for the Brain

Most neurotransmitters, which is to say the molecules that help to send messages from one part of the brain to the other, are peptides or derivatives of peptides. Things like serotonin, norepinephrine, and dopamine, which are the fundamental communication molecules of the central nervous system, are all derivatives of peptides and amino acids. They play the role of final chemical messengers, helping one neuron to communicate with the next in one in the chain so that a signal can move from neuron to neuron across the brain. These molecules are generalists, however, and manipulating them has a global effect on the function of the brain rather than a targeted effect.

Recent research, especially in animals, as revealed that there are other peptides that have more specific functions in the brain than the general neurotransmitters mentioned above. This research is helping to rewrite our understanding of how brain function is controlled and giving us new tools for manipulating everything from sleep quality to memory to mood.

 

A Note on Brain Peptides

As mentioned earlier, the function that was assigned to most brain peptides as a result of early research turns out to not be the major function of most of these peptides. Many peptides are named for their original proposed function and thus often have names that don’t clearly define their major roles in the central nervous system. A good example of this vasoactive intestinal polypeptide or VIP. VIP was originally found in the intestine where it serves to relax smooth muscle contractions and thus increase the flow of blood to certain parts of the gastrointestinal system. VIP has far more diverse function though. In the brain, VIP operates in the pituitary gland to regulate prolactin and growth hormone secretion. Thus, the name vasoactive intestinal polypeptide can be misleading when talking about the central nervous system. Keep this in mind as we discuss peptides for the brain and it will help you transcend the limitations of early research and the often-confusing naming conventions used in this area.

 

Nootropics vs General Brain Peptides

Nootropics are compounds that influence cognition or promote relaxation. They can boost mood, increase attention and memory, improve focus, and enhance creativity and motivation. It is important to note that while all nootropics are active in the brain, not all compounds that function in the brain are nootropics. It is a fine distinction, but one worth considering for readers interested in understanding all of subtle nuances of peptides for brain.

 

Delta Sleep-Inducing Peptide (DSIP)

DSIP is a short, natural peptide first researched in rabbits. As the name suggests, DSIP causes sleep, particularly slow-wave sleep, when introduced into the brain. This is not the only function of DSIP and, in fact, is probably not the most important function of DSIP. Subsequent research shows that this peptide is important in regulating the endocrine system during sleep and thus plays critical roles in growth, stress responses, pain perception, and wound healing.

Research shows that DSIP can significantly alter pain perception and improve mood. It is thought that DSIP acts on central opioid receptors but that it does so indirectly. As such, DSIP has been shown to help reduce withdrawal symptoms following long-term use of pain medications while simultaneously helping to reduce pain[1], [2]. There is hope that a deeper understanding of DSIP will make for the development of better pain management solutions in the future.

 

Epithalon (Epitalon)

Epithalon is a short, synthetic peptide derived from a natural peptide originally isolated from the pineal gland of cows. It is primarily a gene-regulator with effects throughout the body. Often touted as an anti-aging peptide, epithalon is well known for research in rats showing a 27% increase in longevity compared to controls[3].

Epithalon is known to be a gene regulator. In the central nervous system, research suggests that epithalon impacts that function of the pineal gland, retina, and neurons of the brain. Studies show that epithalon increases rates of neurogenesis (the growth of new neurons) and accelerates neuron differentiation[4]. This would suggest that epithalon is a nootropic peptide and may be beneficial in not only prolonging life, but in accelerating learning, protecting memory, and staving off age-related loss of neurons in the brain.

 

Ghrelin and Derivatives

Ghrelin is a natural peptide hormone produced by the gastrointestinal tract that has profound effects on the central nervous system. Ghrelin, often called the hunger hormone, stimulates food intake while simultaneously boosting growth hormone release from the pituitary gland. Research in mice shows that ghrelin, as a result of its actions in the central nervous system, plays important roles in learning, memory, circadian rhythms, reward behavior, and taste sensation. Derivatives of ghrelin, such as ipamorelin, GHRP-2, and GHRP-6 share some or all of these properties in common.

The basic function of ghrelin is to stimulate food intake and concomitant increases in growth hormone levels. By doing this, ghrelin helps to ensure that energy balance favors the accumulation of lean body mass as opposed to fat mass. More subtly, ghrelin influences the types of food we seek out and the rewards (pleasure) we experience from consuming certain foods. Recent animal research shows that ghrelin acts in the brain to regulation connections between food and pleasure as well as food and stress[5].

 

Humanin

Humanin is a natural micro peptide found in mitochondria. Research in rats shows that it is generally cytoprotective, helping to reduce the impact of oxidative stress on cells of the brain, heart, eye, muscle, and blood vessels. In the brain, humanin has been shown to protect against apoptosis in certain oxidative situations. In particular, research in rats shows that humanin can protect neurons in Alzheimer’s disease, prion disease, and other forms of dementia[6], [7].

It appears that humanin works by suppressing the release of Bcl-2 proteins in mitochondria. Astrocytes (cells that support neurons) have been shown to release humanin in response to stress and oxidative damage in the central nervous system[8]. It is thought that enhancing humanin release in the brain may help to reduce age-related memory loss.

The eyes, which are technically an extension of the brain, also benefit from humanin’s activity. Research shows that humanin helps to decrease oxidative stress in the retinal pigment epithelium and improves resistance of this critical tissue layer to apoptosis[9]. This may be important in the setting of ocular conditions like macular degeneration.

 

Pinealon

Pinealon is very short peptide, derived from the pineal gland, that impacts drug metabolism, memory, learning, and circadian rhythm. It is thought to act by altering gene expression levels, much like epithalon.

Research in rats shows that pinealon protects neurons from death following injury and acts as an antioxidant in some settings. Like many nootropic peptides, pinealon appears to protect neurons against excitotoxic damage. Specifically, pinealon increases levels of another peptide called irisin. Irisin is important in neuron proliferation and differentiation. Higher levels of irisin have been linked to improved memory and cognition. In fact, irisin may be one of the molecules that modulates the beneficial impact of exercise on the central nervous system[10].

 

Semax

Semax is a synthetic derivative of adrenocorticotropic hormone (ACTH). It has been found to regulate gene expression in the immune system, regulate pain responses, modulate the function of the liver, and benefit both heart and brain function.

Semax appears to beneficially affect brain-derived neurotropic factor (BDNF) in the setting of injury. Research shows that it can improve treatment and recovery following stroke and that it aids in both learning and memory formation in healthy rats. Semax appears to boost BDNF levels in the forebrain, which helps with long-term retention of information[11]. Work in rats also suggests that Semax activates the default mode network, which is a complex array of brain regions that helps to regulate concentration, planning, memory, and our sense of self[12].

 

Selank

Selank is a short, anxiolytic peptide developed in Russia. It is a synthetic analogue of tuftsin and thus has immune modulating properties in addition to its effects on monoamine neurotransmitters and brain-derived neurotropic factor (BDNF). Research shows that Selank has strong anti-anxiety and neuroprotective properties in the setting of anxiety as a result of its agonist activity on GABAA receptors of the central nervous system.

Selank also has positive benefits on learning, memory, mood, and stress levels. It is widely considered a nootropic because of its ability to increase levels of BDNF, which promotes the growth and differentiation of neurons in the brain. Research shows that Selank increases memory stability and enhances memory storage in mouse models[13]. Studies in rats indicate that Selank changes the expression levels of more than 36 different genes in the central nervous system and may modulate ion-dependent processes in learning and memory[14]. There is even research showing that Selank can rescue memory following brain damage in rats by inhibiting catecholamine-induced excitotoxic damage[15]. As such Selank is under investigation for use in acute brain injury caused by stroke, trauma, and more.

 

Vasoactive Intestinal Polypeptide (VIP)

Despite the name, VIP is a peptide that has extensive activity in the central nervous system. Research in animals shows that VIP

• Regulates the secretion of prolactin and growth hormone,

• Protects neurons against ischemia (reduced blood supply) and oxidative stress, and

• Helps to synchronize the central nervous system with light cues for regulating circadian rhythms.

VIP acts as a neurotransmitter, neurotrophic, and anti-inflammatory in the central nervous system. Research shows that it is important in maintaining the blood-brain barrier (BBB), which makes VIP important in regulating what enters and exits the central nervous system[16].

VIP has also been shown to regulate the accumulation of beta amyloid in mouse models of Alzheimer’s disease. It is also an important neuroprotectant in a number of central nervous system disorders including Parkinson’s disease and other excitotoxic neurological conditions like multiple sclerosis[17]–[19]. VIP appears to help shift immune system balance away from inflammatory Th1 responses toward anti-inflammatory Th2-reponses[20].

In addition to its benefits in the central nervous system, VIP has important protective properties in the heart, lungs, and GI tract. VIP may be one of the most important discoveries in preventing long-term pulmonary remodeling in conditions like cystic fibrosis, pulmonary hypertension, COPD, and other serious lung diseases.

 

Peptides for Brain: Summary

Science is making ever-greater strides in understanding the role of peptides for brain function. As it turns out, much of what we learned in the past was limited by the types of tools available to scientists. With the advent of newer methods of probing the brain, we have come to learn that peptides more important in cognitive function than we ever knew. Additionally, we have gained a greater understanding of the specific roles of these peptides and a more nuanced view of how they work both in the brain and throughout the body. Above are many of the most important peptides for brain function, but the list is hardly exhaustive and serves only to highlight certain properties of the peptides listed. A more thorough examination of the research into peptides for brain is in order for anyone interested in the nuances of how these peptides can modulate, both on their own and in combination, the function and development of the brain.

 

Resources

[1]W. Larbig, W. D. Gerber, M. Kluck, and G. A. Schoenenberger, “Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study,” Eur. Neurol., vol. 23, no. 5, pp. 372–385, 1984, doi: 10.1159/000115716.

[2]A. Nakamura, M. Nakashima, T. Sugao, H. Kanemoto, Y. Fukumura, and H. Shiomi, “Potent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP),” Eur. J. Pharmacol., vol. 155, no. 3, pp. 247–253, Oct. 1988, doi: 10.1016/0014-2999(88)90510-9.

[3]V. N. Anisimov, S. V. Mylnikov, and V. K. Khavinson, “Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats,” Mech. Ageing Dev., vol. 103, no. 2, pp. 123–132, Jun. 1998, doi: 10.1016/S0047-6374(98)00034-7.

[4]V. Khavinson et al., “AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism,” Mol. Basel Switz., vol. 25, no. 3, p. E609, Jan. 2020, doi: 10.3390/molecules25030609.

[5]M. Perelló and J. M. Zigman, “The Role of Ghrelin in Reward-Based Eating,” Biol. Psychiatry, vol. 72, no. 5, Art. no. 5, Sep. 2012, doi: 10.1016/j.biopsych.2012.02.016.

[6]M. Matsuoka, “Humanin; a defender against Alzheimer’s disease?,” Recent Patents CNS Drug Discov., vol. 4, no. 1, Art. no. 1, Jan. 2009, doi: 10.2174/157488909787002609.

[7]I. Sponne, A. Fifre, V. Koziel, B. Kriem, T. Oster, and T. Pillot, “Humanin rescues cortical neurons from prion-peptide-induced apoptosis,” Mol. Cell. Neurosci., vol. 25, no. 1, Art. no. 1, Jan. 2004, doi: 10.1016/j.mcn.2003.09.017.

[8]S. C. Zárate, M. E. Traetta, M. G. Codagnone, A. Seilicovich, and A. G. Reinés, “Humanin, a Mitochondrial-Derived Peptide Released by Astrocytes, Prevents Synapse Loss in Hippocampal Neurons,” Front. Aging Neurosci., vol. 11, p. 123, 2019, doi: 10.3389/fnagi.2019.00123.

[9]P. G. Sreekumar et al., “The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction,” Invest. Ophthalmol. Vis. Sci., vol. 57, no. 3, pp. 1238–1253, Mar. 2016, doi: 10.1167/iovs.15-17053.

[10]J. Zhang and W. Zhang, “Can irisin be a linker between physical activity and brain function?,” Biomol. Concepts, vol. 7, no. 4, pp. 253–258, Aug. 2016, doi: 10.1515/bmc-2016-0012.

[11]“Semax, an analogue of adrenocorticotropin (4–10), binds specifically and increases levels of brain‐derived neurotrophic factor protein in rat basal forebrain - Dolotov - 2006 - Journal of Neurochemistry - Wiley Online Library,” May 08, 2021. https://onlinelibrary.wiley.com/doi/full/10.1111/j... (accessed May 08, 2021).

[12]I. S. Lebedeva et al., “Effects of Semax on the Default Mode Network of the Brain,” Bull. Exp. Biol. Med., vol. 165, no. 5, Art. no. 5, Sep. 2018, doi: 10.1007/s10517-018-4234-3.

[13]T. P. Semenova, I. I. Kozlovskiĭ, N. M. Zakharova, and M. M. Kozlovskaia, “[Experimental optimization of learning and memory processes by selank],” Eksp. Klin. Farmakol., vol. 73, no. 8, Art. no. 8, Aug. 2010.

[14]T. A. Kolomin et al., “[Transcriptome alteration in hippocampus under the treatment of tuftsin analog Selank],” Zh. Vyssh. Nerv. Deiat. Im. I. P. Pavlova, vol. 63, no. 3, pp. 365–374, Jun. 2013, doi: 10.7868/s0044467713030052.

[15]T. P. Semenova, M. M. Kozlovskaya, N. M. Zakharova, I. I. Kozlovskii, and A. V. Zuikov, “Effect of selank on cognitive processes after damage inflicted to the cerebral catecholamine system during early ontogeny,” Bull. Exp. Biol. Med., vol. 144, no. 5, pp. 689–691, Nov. 2007, doi: 10.1007/s10517-007-0406-2.

[16]D. R. Staines, E. W. Brenu, and S. Marshall-Gradisnik, “Postulated vasoactive neuropeptide immunopathology affecting the blood–brain/blood–spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment?,” Neuropsychiatr. Dis. Treat., vol. 5, pp. 81–89, 2009.

[17]F. R. O. de Souza, F. M. Ribeiro, and P. M. d’ Almeida Lima, “Implications of VIP and PACAP in Parkinson’s disease: what do we know so far?,” Curr. Med. Chem., Mar. 2020, doi: 10.2174/0929867327666200320162436.

[18]O. T. Korkmaz et al., “Vasoactive Intestinal Peptide Decreases β-Amyloid Accumulation and Prevents Brain Atrophy in the 5xFAD Mouse Model of Alzheimer’s Disease,” J. Mol. Neurosci. MN, vol. 68, no. 3, Art. no. 3, Jul. 2019, doi: 10.1007/s12031-018-1226-8.

[19]P. Gressens, L. Besse, P. Robberecht, I. Gozes, M. Fridkin, and P. Evrard, “Neuroprotection of the developing brain by systemic administration of vasoactive intestinal peptide derivatives,” J. Pharmacol. Exp. Ther., vol. 288, no. 3, Art. no. 3, Mar. 1999.

[20]R. L. Mosley et al., “A Synthetic Agonist to Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities in Models of Parkinson’s Disease,” Front. Cell. Neurosci., vol. 13, p. 421, 2019, doi: 10.3389/fncel.2019.00421.

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Your Agreement to Abide by All Applicable Laws

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Relationship between www.PeptideSciences.com and Users.

www.PeptideSciences.com and users of our Site are independent contractors, and no agency, partnership, employment or other relationship is created or is intended to be created by the use of our Web Site.

Governing Law and Jurisdiction

This Web Site (excluding linked sites, if any) is administered and controlled by www.PeptideSciences.com and its affiliates, subsidiaries, officers, directors, employees or agents from its offices in the accordance with the laws of Nevis. You agree that this Terms and Conditions of Use Agreement and this Web Site will be governed by and construed in accordance Nevis law without giving effect to any principles of conflicts of laws. You access this Web Site and/or associated services of www.PeptideSciences.com at your own risk, and remain responsible for complying with the laws of the jurisdiction within which you are located.

Prices; Payment Terms; Interest

The prices for the products and services on this Web Site are quoted, for convenience, in United States dollars and shall be as set forth in this Web Site as at the time of acceptance of an order by www.PeptideSciences.com. Prices for Products shall be subject to change without any further notice. Credit terms are within www.PeptideSciences.com's sole discretion, and unless otherwise specified in www.PeptideSciences.com's invoice, payment must be received by www.PeptideSciences.com prior to www.PeptideSciences.com's acceptance of an order.

Consequences

www.PeptideSciences.com reserves the right to suspend or terminate your account if you violate the Terms of Use Agreement. If your violation causes harm to others, you agree to indemnify and hold www.PeptideSciences.com harmless from and against any and all loss, damage, or expense. If any dispute arises between us regarding this Agreement or your use of this Web Site, it shall be resolved through good faith negotiations between the parties.

Entire Agreement

These Terms and Conditions and any terms incorporated or referred to herein constitute the entire agreement between www.PeptideSciences.com and you relating to your use of this Web Site and the subject matter hereof, and supersede any prior understandings or agreements (whether electronic, oral or written) regarding the subject matter, and may not be amended or modified except in writing, or by www.PeptideSciences.com making such amendments or modifications in accordance with this Terms and Conditions of Use Agreement.

Severability

If any part of this Terms and Conditions of Use Agreement is deemed or determined to be unenforceable, then such part shall be eliminated or limited to the minimum extent necessary. The remainder of this Terms and Conditions of Use Agreement, including any revised portion, shall remain and be in full force and effect. This Terms and Conditions of Use Agreement are the entire agreement between us governing your use of this Web Site.

Headings

The headings contained in this Terms and Conditions of Use Agreement and the www.PeptideSciences.com Privacy Policy are for reference only.

Force Majeure

www.PeptideSciences.com shall not be liable for any delay or failure in performance caused by circumstances beyond its reasonable control, including, without limitation, delays due to backorders of requested products, mail delays, customs delays or lost shipments. www.PeptideSciences.com shall not be responsible to notify the Customer in the event of such delays. The Customer shall be solely responsible to make other arrangements to purchase alternative products and any costs incurred in connection with such purchases.

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Complete Agreement

Except as expressly provided in a particular "legal notice" on this Site, these Terms and Conditions constitute the entire agreement between you and this Site with respect to the use of this Site, and Content. By clicking “I agree” when placing your order, you agree with ALL OF OUR TERMS and CONDITIONS as stated above as well as our Shipping and refunds Policy.

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