Research
FOXO4-DRI Peptide Structure
| Molecular formula: | C228H388N86O64 |
| Molecular weight: |
5358 g/mol
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| PubChem CID: | 167312269 |
| Synonyms |
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| Research Applications: |
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What is FOXO4-DRI?
FOXO4 D-Retro-Inverso is a cell-penetrating peptide designed to disrupt the interaction between the FOXO4 protein and p53, a key regulator of cell death and senescence. The peptide has been used in scientific research to selectively induce apoptosis of senescent cells, which are cells that have stopped dividing and contribute to aging and various diseases.
FOXO4-DRI and Aging
FOXO4-DRI has been shown to counteract general signs of aging, such as hair loss and frailty, in fast-aging mice. This suggests a broader potential for FOXO4-DRI in mitigating various age-related conditions by targeting and removing senescent cells [R].
Studies showed that FOXO4-DRI improved kidney function in aged mice by reducing the number of senescent cells. This was observed in both naturally aged mice and those with induced liver damage, suggesting that the peptide can restore tissue health by targeting senescent cells [R].
In aged mice, FOXO4-DRI was found to alleviate age-related testosterone secretion issues by eliminating senescent Leydig cells in the testes. This improved the testicular environment and increased testosterone production, highlighting its potential for treating male late-onset hypogonadism [R,ย R].
FOXO4-DRI also showed promise in removing senescent cells from human chondrocytes, which are cells found in cartilage. This could enhance the quality of cartilage and improve outcomes for treatments like autologous chondrocyte implantation, used in joint repair [R].
FOXO4-DRI and Chemotherapy-Induced Senescence
Chemotherapy drugs like Doxorubicin can cause cells to become senescent, leading to long-term health issues and accelerated aging. FOXO4-DRI has been shown to counteract this effect by inducing apoptosis (cell death) in these senescent cells, thereby reducing chemotoxicity and improving tissue function [R].
FOXO4-DRI works by binding to p53, preventing it from interacting with FOXO4. This causes p53 to be excluded from the nucleus and directed to the mitochondria, where it triggers apoptosis in senescent cells. This mechanism has been effective in both in vitro (lab) and in vivo (animal) models [R,ย R].
FOXO4-DRI and Osteoarthritis
In studies related to osteoarthritis (OA), FOXO4-DRI has shown promise in reducing the levels of senescence markers in chondrocytes, the cells found in cartilage. This treatment led to decreased expression of proteins associated with inflammation and cartilage breakdown, such as MMP12 and MMP13, and increased expression of SOX9, which is important for cartilage health. Although FOXO4-DRI did not significantly improve the regenerative potential of chondrocytes, it effectively reduced the number of senescent cells, which could help slow the progression of OA [R].
FOXO4-DRI and Fibrosis
In mouse models of pulmonary fibrosis (PF) induced by bleomycin, FOXO4-DRI treatment led to milder lung damage and reduced collagen deposition. It works by disrupting the FOXO4-p53 complex, which helps in the nuclear exclusion of p53, a protein involved in cell cycle regulation. This action decreases the total ECM protein content and alleviates fibrosis symptoms [R,ย R].
FOXO4-DRI also reduces the number of myofibroblasts, which are cells that play a key role in ECM production and fibrosis. With its ability to decrease these cells, FOXO4-DRI helps lower ECM receptor interactions and fibrosis progression [R].
FOXO4-DRI and Cancer
As mentioned above, FOXO4-DRI binds to p53, preventing it from interacting with FOXO4. This causes p53 to leave the nucleus, leading to cell death in senescent cells.
In mouse models, FOXO4-DRI has been shown to reduce the negative effects of chemotherapy, such as liver damage, and improve overall health by eliminating senescent cells [R].
The peptide has also been tested in various cancer cell cultures, including melanoma, colorectal, and breast cancer. It effectively killed senescent cancer cells without harming normal dividing cells. Research has also explored using FOXO4-DRI with other treatments, like dabrafenib, to enhance its effectiveness in killing cancer cells [R,ย R].
