P21 Dosage

P21 is a tetrapeptide, better known as a synthetic mimetic of ciliary neurotrophic factor (CNTF). It is a naturally occurring molecule that influences the growth of neurons. Receptors for this peptide also exist in other tissues, such as bone, but its effects have primarily been studied in nervous tissue. Neuronal growth and control of neurotransmitter synthesis are its primary properties, which are why the peptide may help treat nervous diseases. Additionally, it may protect neurons and other supporting cells in that tissue from the damaging effects of inflammation and its spread. This property is the basis for the treatment and prevention of Alzheimer's disease. Scientists believe that P21 may also affect the Hypothalamus (a part of the brain responsible for regulating information about food intake), increasing the feeling of satiety, which consequently leads to weight loss. The original CNTF is unstable, has a poor pharmacological profile, and will induce the formation of antibodies to its molecule. The modified version, in the form of the P21 molecule, does not exhibit these bad properties and represents a much more effective option.

Dosage Chart

About the Peptide

P21 is a tetrapeptide known as a modified synthetic mimetic of ciliary neurotrophic factor (CNTF). The original natural molecule is best known for its effect on neuronal growth and stimulation of neurogenesis. It can also prevent the further spread of infection through tissue or mitigate the release of its harmful effects, as presented through symptoms. This molecule has shown an inferior pharmacological profile, many side effects, and an increased chance of antibody formation. Additionally, it has been demonstrated in various studies to be unstable in tissue. The chemical structure of the P21 peptide has been significantly modified compared to the primary version, primarily in the reduction in the number of amino acids, which has led to improved efficiency and the elimination of the aforementioned negative aspects.

Due to its neuroprotective functions, scientists assume that the peptide may be effective in treating Alzheimer's disease, a severe neurodegenerative disease with dementia as the primary symptom. This disease is characterized by the accumulation of beta-amyloid plaques and the formation of accumulated tau protein. This pathogenesis most often leads to neurodegeneration and the death of neurons that have no chance of regeneration. It is believed that P21, through various mechanisms of action, can partially repair the damage and significantly prevent further development of the disease. Scientific studies have demonstrated that P21 has the potential to influence the dentate gyrus, a region that plays a pivotal role in information processing and pattern formation. This property is key because the patterns created allow us to distinguish one memory from another.

In patients diagnosed with neurodegenerative diseases, particularly Alzheimer's disease, cognitive function decline occurs. A clear symptom of dysfunction is noticeable dementia in these patients, but after that comes the inability to draw conclusions based on information, incomprehensible speech and understanding, decreased attention, or failure to focus. Additionally, the learning and perception processes are significantly impaired.

These symptoms occur as a result of the accumulation of tau protein and the deposition of beta-amyloid plaques. Scientists believe that by improving memory through various mechanisms of action, P21 may also act on other cognitive errors. This property may be key in treating not only Alzheimer's disease but also many different conditions that have some cognitive dysfunctions in their symptomatology.

Based on scientific findings, it is assumed that P21 can suppress appetite and increase the feeling of satiety. As a result of reduced food intake, weight loss occurs, which could serve as the basis for treating obesity.

List of Uses

The Impact of the P21 Peptide on Alzheimer's Disease

Alzheimer's disease is a severe neurodegenerative disease primarily characterized by dementia and is also one of the leading causes of memory loss, particularly among the elderly population. The effect of the peptide is mainly investigated on nervous tissue, but it can act anywhere where neurons are present, such as bone tissue.
The body's initial reaction to neuronal damage and synapse rupture (caused by inflammation) is increased activity in the dentate gyrus in the central nervous system. However, in most cases, there is no possibility of shifting the balance in favor of neurogenesis. After the administration of P21, the gyrus is even more activated, overcoming the barrier and potentiating neurogenesis. In this way, a new number of neurons is created, capable of processing information and forming an accurate picture of reality. This is one of the mechanisms of action responsible for repairing the damage caused during the disease development process. It is believed that the combination of these properties, and in particular the activation of the dentate gyrus, stimulates the formation of new episodic memories and the ability to perceive the present. This part of the temporal lobe is crucial for processing information and creating patterns, which allows patients to distinguish one memory from another.

In addition to its beneficial effects on the further course of the disease, P21 may act on apoptosis, reducing the rate of neuronal death, as well as limiting further inflammation and protecting the nervous system from harmful effects. With these functions, the peptide may also help treat other inflammatory and neurodegenerative diseases of similar etiology.

Impact on Cognitive Defects

Cognition encompasses numerous processes that are responsible for acquiring knowledge and learning. In neurodegenerative diseases such as Alzheimer's disease, memory is primarily affected, but other cognitive defects also appear, making these patients susceptible to unusual behavior. In addition to memory loss, patients diagnosed with AD also experience attention and focus disorders, where they cannot stay on specific information, making plans, organization, and decision-making is almost impossible. Language use, comprehension, perception, and learning are also affected, so these patients are unable to function independently.

As a result of a similar mechanism of action, positive effects on cognition are observed. Regardless of the memory loss itself, in scientific studies, subjects generally reported better focus and an increased ability to make decisions and draw conclusions from the information they heard, all of which occurred after taking P21. This could provide an excellent basis for further research into the effects of peptides on diseases characterized by another cognitive defect as the primary symptom, such as attention disorders.

Food Intake

Although there are still not enough studies to confirm this beneficial effect, scientists assume that P21 could reduce food intake, increasing satiety, thus delaying the feeling of hunger. The mechanism of action should be based on increased concentrations of the central molecule (CNTF), which leads to greater production of alpha melanocytes, which act on biochemical pathways activated after eating. As a result, a sustained feeling of satiety appears, and neurogenesis only further increases this property. If the effect on food intake is confirmed, it could be an excellent basis for obesity therapy.

Dosage Calculator

The dose and method of application vary depending on the indication but are generally precisely defined. The goal of peptide administration is mainly to improve cognitive performance and treat neurodegenerative diseases such as Alzheimer's disease. In this case, the optimal dose in the first three weeks should be 100-250mcg, administered via subcutaneous injection once a day. Later, the maintenance dose may be slightly higher but should not exceed 500 mcg per day. The method of administration remains the same throughout therapy and should not be changed independently of the treatment. The injection region is usually the abdomen, but to avoid side effects such as injection site reactions, the area can be changed. Therapy should not last longer than six weeks unless approved by the doctor.

Conclusion

P21 is a synthetic mimetic of ciliary neurotrophic factor and may have several beneficial effects. Some of the most significant are the improvement of cognitive performance and the potential treatment of Alzheimer's disease. Additionally, it is possible to influence food intake. If used as indicated with an optimal dose, the peptide should exert all of its intended effects. Regardless of the achievements to date, P21 will undoubtedly be the subject of future research.

References:

1. Baazaoui, N., & Iqbal, K. (2017). Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound. Alzheimer's research & therapy, 9(1), 45. https://doi.org/10.1186/s13195-017-0273-7
2. Baazaoui, N., & Iqbal, K. (2017). Prevention of Amyloid-β and Tau Pathologies, Associated Neurodegeneration, and Cognitive Deficit by Early Treatment with a Neurotrophic Compound. Journal of Alzheimer's disease : JAD, 58(1), 215–230. https://doi.org/10.3233/JAD-170075
3. Liu, Y., Wei, W., Baazaoui, N., Liu, F., & Iqbal, K. (2019). Inhibition of AMD-Like Pathology With a Neurotrophic Compound in Aged Rats and 3xTg-AD Mice. Frontiers in aging neuroscience, 11, 309. https://doi.org/10.3389/fnagi.2019.00309
4. Bolognin, S., Buffelli, M., Puoliväli, J., & Iqbal, K. (2014). Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compound. Neurobiology of aging, 35(9), 2134–2146. https://doi.org/10.1016/j.neurobiolaging.2014.02.017
5. Rockenstein E, Mante M, Adame A, Crews L, Moessler H, Masliah E. Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer's disease. Acta Neuropathol. 2007 Mar;113(3):265-75. doi: 10.1007/s00401-006-0166-5. Epub 2006 Nov 28. PMID: 17131129.
6. Iqbal K, Kazim SF, Bolognin S, Blanchard J. Shifting balance from neurodegeneration to regeneration of the brain: a novel therapeutic approach to Alzheimer's disease and related neurodegenerative conditions. Neural Regen Res. 2014 Aug 15;9(16):1518-9. doi: 10.4103/1673-5374.139477. PMID: 25317168; PMCID: PMC4192968.
7. N. Baazaoui and K. Iqbal, “Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound,” Alzheimers Res. Ther., vol. 9, Jun. 2017, doi: 10.1186/s13195-017-0273-7.