FOXO4-DRI (Proxofim) (10mg)

FOXO4-DRI Peptide

FOXO4-DRI is a synthetic version of FOXO4, containing D amino acids instead of L amino acids. This modification is intended to allow the peptide to retain the functionality of the original protein but with a longer shelf life and lower clearance. Its most prominent function has been suggested to be the regulation of apoptosis in senescent cells^[1]. It appears to inhibit FOXO4-p53 binding, thereby p53 may target pro-apoptotic genes and promote their expression. These proteins, in turn, may bring about apoptosis of old cells, thereby reducing the old cell burden in tissues. This may lead to increases in cellular differentiation and tissue repair. FOXO4 protein is a prominent member of the group of transcription factors that have been classified as exhibit potential to regulate growth and differentiation. It appears to be endogenously abundant in tissues such as the placenta, ovaries, fat cells, testes, and adrenal glands. Post-translational modifications, especially those in the DNA binding domain of FOXO4 protein, appear to modify its functionality as a transcription factor and regulation of pathways such as apoptosis, cellular senescence, insulin signaling, and senescence.

FOXO4-D-Retro-Inverso is a synthetic ad partially altered form of the original FOXO4 protein. The modification was developed to help enhance the half-life of the protein and allow it to obstruct the normal FOXO4 function. FOXO4-DRI has been suggested to prevent normal FOXO4 binding to p53, eliminating of senescent cells, enhancing organ function, and reducing the progression of cell death. FOXO4-DRI appears to influence insulin signaling, cell cycle regulation, and oxidative stress signaling pathways. The peptide appears to be permeable into cells and has been suggested by researchers to selectively induce senescent cell apoptosis based off of results found in animal studies.

Specifications

Other Known Titles: Forkhead box protein O4, Proxofim, FOXO4a, AFX, AFX1, MLLT7

Sequence: H-D-Leu-D-Thr-D-Leu-D-Arg-D-Lys-D-Glu-D-Pro-D-Ala-D-Ser-D-Glu-D-Ile-D-Ala-D-Gln-D-Ser-D-Ile-D-Leu-D-Glu-D-Ala-D-Tyr-D-Ser-D-Gln-D-Asn-D-Gly-D-Trp-D-Ala-D-Asn-D-Arg-D-Arg-D-Ser-D-Gly-D-Gly-D-Lys-D-Arg-D-Pro-D-Pro-D-Pro-D-Arg-D-Arg-D-Arg-D-Gln-D-Arg-D-Arg-D-Lys-D-Lys-D-Arg-D-Gly-OH

Molecular Formula: C₂₂₈H₃₈₈N₈₆O₆₄

Molecular Weight: 5358.05 g/mol

FOXO4-DRI Research

DRI peptides are synthetic variants of their natural counterparts. The synthetic alternatives have the sequence of amino acids reversed as well as the alpha chirality changed^[2]. Naturally occurring amino acids have L chiral configuration, while the DRI peptides appear to be composed of D chiral amino acids. This has the potential to protect the synthetic peptides from enzymatic degradation. This may lead to prolonged functional viability. They are also potential candidates for peptidomimetics for the study of protein-protein, protein-peptide, and peptide-peptide interactions.

FOXO4-DRI and Research in Cell Aging, Senescence
FOXO4 is suggested to help the perpetuation of aged or senescent cells. It appears to bind to p53 and thereby may prevent apoptotic death of the senescent cells^[3]. The DRI peptide appears to prevent FOXO4-p53 interaction, thus p53 may activate apoptotic protein and induce cellular death. Thus the old cells may be cleared from tissues, naturally allowing for better tissue regeneration. Studies have observed exposing aging mice with the DRI peptide reportedly resulted in improved tissue regeneration and healthspan. Healthspan refers to the tenure of lifespan wherein the cell body remains active. It decreases with age. Tissue renewal may certainly reduce the biological aging of tissues and thereby enhance healthspan. The aged mice exhibited a longer healthspan, exerted greater physical activity, and researchers observed less disability such as cardiac diseases and musculoskeletal dysfunction, etc.

FOXO4-DRI and Research in Insulin Signal Regulation
FOXO proteins are suggested to regulate the influence of insulin signaling and insulin-like growth factors. Scientific data suggests that the FOXO family of proteins may act downstream of insulin signaling to regulate cellular growth, metabolism, differentiation, and oxidative stress. Mutations in FOXO genes have been suggested to cause diabetic toxicity such as hyperglycemia and hyperlipidemia and may even lead to cancer. In the context of diabetes, it may lead to heart attack, impaired wound healing, stroke, and kidney damage, to name a few.^[4] The exact mechanism of FOXO4-DRI signaling is yet unknown. It is opined to reduce fasting blood sugar levels.

FOXO4-DRI and Research in Heart Disease
Cell age and death is one of the critical factors which influence the onset of cardiac disease. The reason has been ascribed to loss of proteasome activity with age. Proteasome helps in the degradation of oxidized, modified, or damaged proteins, thereby keeping the cellular environment functional. Reduction in proteasome functionality may lead to the accumulation of toxic protein, which can be detrimental to cardiac tissues^[5]. FOXO signaling appears to have the potential to increase autophagy and proteasomal activity in the heart, and the clearing out damaged cells. It has been suggested that FOXO4-DRI protein or a variant of it may promote proteasomal functions, enhancing the function of cardiac tissues and reducing the risk of cardiovascular disease.

FOXO4-DRI and Research in Neurodegenerative Diseases
The complex etiology of neurodegenerative diseases is yet to be completely understood. There is research data that indicates the alteration in FOXO proteins may be a contributor to the disease etiology^[6]. A decrease in proteasomal activity appears to enhance the underlying condition of Huntington’s disease, Alzheimer’s disease, Parkinson’s, and Prion disease. Hence, FOXO-DRI protein or other modified alternatives may be valuable in research of certain neurodegenerative conditions by substituting the absence of native FOXO proteins.

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