FOXO4-DRI is a synthetic variant of the FOXO4 protein designed to be biochemically equivalent to the endogenously accessible FOXO4 protein. Forkhead box O transcription factor 4-D-Retro-Inverso peptide (Proxofim) is an abbreviation for this protein's full scientific name. The structure of the FOXO4-DRI peptide is identical to that of the FOXO4 protein, except for the L amino acids.
FOXO4-DRI Peptide Overview
The D- and L-amino acid structures are switched to create retro inverso peptides (DRI peptides), linear chains of amino acids with a "reversed" sequence. D amino acids are the mirror image of L amino acids found in all proteins. The major potential property of replacing L amino acid with D amino acid is that the protein structure might subsequently be more stable.Studies suggest preventing the FOXO4 protein from attaching to the p53 protein [ii] is the primary focus of research into the FOXO4-DRI peptide. Researchers speculate cell cycle progression and death are controlled by the p53 protein, an endogenous regulator protein. Research suggests that the FOXO4 protein may prevent the p53 from binding with DNA, and so apoptosis and cell death. Scientists hypothesize this step may be blocked by the FOXO4-DRI peptide, enabling p53 to connect with DNA and promote cell death.
Research suggests senescent cells, which have become dysfunctional due to age, may be the only cells on which FOXO4-DRI peptide appears to exert this potential. Tissue function may be enhanced due to this biological mechanism, which might promote cell proliferation and differentiation. The following regions of action for this peptide have been investigated:
- Potential induction of cellular senescence
- Prospective anti-aging action
- Possible role in the insulin signaling pathway
- Possible cardial protection
- Potentially reduces the severity of neurological impairment
FOXO4-DRI Peptide Research and Clinical Investigations
FOXO4-DRI Peptide and Senescence
Recent studies on the peptide FOXO4-DRI suggest it may not be able to halt cell senescence completely, but it may slow it down by blocking the senescence pathway initiated by FOXO4 in the first place. Research suggests this peptide may improve cell regeneration by decreasing senescence and cellular damage. In a 2017 experiment [iii], the protein combination and a placebo were given to elderly mice models. Increased fitness, enhanced renal function, and denser fur were all results that appeared to be present in test animals following the study.FOXO4-DRI Peptide and the Heart
Proteasome enzyme levels decline with age, according to research published in 2002 [iv]. These enzymes are thought to play a crucial part in eliminating cells that have been deemed damaged or defective. Studies suggest the FOXO4 protein found in nature seems to modulate proteasome enzyme levels; however, this does not guarantee that it will aid in reducing damaged cells. Researchers have hypothesized that a peptide called FOXO4-DRI may stimulate healthy processes while simultaneously killing off defective cells.FOXO4-DRI Peptide and Insulin Signaling
Recent studies [v] have suggested that FOXO proteins may mediate the insulin signaling pathway, controlling the insulin's inhibitory activities in cell metabolism, cell cycle, oxidative stress, senescence, and aging. Researchers have speculated that FOXO4-DRI peptide may increase the downstream impact of insulin, resulting in lower blood sugar levels, but further study is needed to establish this.FOXO4-DRI and Neurological Activity
Researchers speculate that alterations in proteasome enzyme activity over time may contribute to cognitive impairment, although the exact pathophysiology of many neurological disfunction is unknown. It has been hypothesized [vi] that neurological disfunction is associated with reduced proteasome activity. This downregulation may not be the only cause of the issue, but its role is widely considered to be impactful by researchers. Researchers have reported data in subjects with neurodegenerative issues (NDDs) may have had altered quantities of FOXO proteins in the brain [vii]. As a result of these findings, it has been hypothesized that FOXO4-DRI peptide might aid in maintaining healthy levels of FOXO proteins and halting the development of any NDDs linked to this pathway.FOXO4-DRI and Hypogonadism
The potential of FOXO4-DRI peptide in test subjects with late-onset hypogonadism was investigated in recent research studies [viii]. A senescent Leydig cell in vitro model was employed for the purpose of this experiment. In order to induce senescence, these Leydig cells were extracted from male mice and treated with hydrogen peroxide. Researchers speculated that FOXO4 cells appeared to aid in the survival of these injured cells and maybe prevent apoptosis. These senescent Leydig cells were reported to undergo apoptosis after exposure to the FOXO4-DRI peptide, inhibiting FOXO4 proteins by enabling p53 to connect with DNA. Research studies suggest FOXO4-DRI peptide may enhance Leydig cell activity [viii] in normally aged mice.More investigation is required to explore its potential in scientific research, and these studies must continue. Only academic and scientific institutions are allowed to use FOXO4-DRI peptides for sale. Please note that none of the items mentioned are approved for human or animal ingestion. Laboratory research compounds are only for in-vitro and in-lab use. Any kind of physical introduction is illegal. Only authorized professionals and working scientists may make purchases. The content of this piece is intended only for instructional purposes.
References
[i] Sun, Yan et al. "FOXO4 Inhibits the Migration and Metastasis of Colorectal Cancer by Regulating the APC2/ß-Catenin Axis." Frontiers in cell and developmental biology vol. 9 659731. 23 Sep. 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495124/
[ii] Zhang, C., Xie, Y., Chen, H., Lv, L., Yao, J., Zhang, M., Xia, K., Feng, X., Li, Y., Liang, X., Sun, X., Deng, C., & Liu, G. (2020). FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging, 12(2), 1272-1284. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053614/
[iii] Marjolein P. Baar et al, Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Vol 169 Issue 1, https://doi.org/10.1016/j.cell.2017.02.031
[iv] Anne-Laure Bulteau, Luke I. Szweda, Bertrand Friguet, Age-Dependent Declines in Proteasome Activity in the Heart, Archives of Biochemistry and Biophysics, Volume 397, Issue 2, 2002, Pages 298-304, ISSN 0003-9861, https://doi.org/10.1006/abbi.2001.2663
[v] Lee, S., & Dong, H. H. (2017). FoxO integration of insulin signaling with glucose and lipid metabolism. The Journal of endocrinology, 233(2), R67-R79. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480241/
,br>[vi] Ciechanover A, Brundin P. The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron. 2003 Oct 9;40(2):427-46. https://pubmed.ncbi.nlm.nih.gov/14556719/
[vii] Wei Hu, Zhi Yang, Wenwen Yang, Mengzhen Han, Baoping Xu, Zihao Yu, Mingzhi Shen, Yang Yang, Roles of forkhead box O (FoxO) transcription factors in neurodegenerative diseases: A panoramic view, Progress in Neurobiology, Volume 181, 2019, 101645, ISSN 0301-0082, https://doi.org/10.1016/j.pneurobio.2019.101645
[viii] Zhang, C., Xie, Y., Chen, H., Lv, L., Yao, J., Zhang, M., Xia, K., Feng, X., Li, Y., Liang, X., Sun, X., Deng, C., & Liu, G. (2020). FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging, 12(2), 1272-1284. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053614/