Thymosin beta 4

Background

Thymosins are lymphoid growth factors that were first isolated by Goldstein and White from the thymus of a calf in 1966. Based on the isoelectric point (pI), thymosins can be classified into α (pI < 5.0), β (5.0 < pI <7.0) and γ (pI > 7.0) types. Among these types, thymosin β, characterized by sequestration of globular actin (G‐actin) monomers, is highly conserved at the amino acid sequence level in species ranging from echinoderms to mammals. Currently, 16 thymosin β members have been reported; among these, Thymosin beta 4 (Tβ4), thymosin β10 (Tβ10) and thymosin β15 (Tβ15) have been identified and isolated in mammals. Studies have shown that Tβ4, accounting for more than 70% of all thymosins, is found ubiquitously in mammalian body fluids, tissues and cells (except erythrocytes) and can be detected in both the nucleus and cytoplasm[1].

Description

Thymosin β-4 is an endogenous pro-angiogenic, fibroblast-activating peptide that is involved in hormone regulation. Thymosin β-4 also exhibits immunomodulatory and cardioprotective activities. Thymosin β-4 improves would healing in cardiac issue and improves cardiac function in vivo. Thymosin β-4 binds G-actin filaments, preventing actin polymerization.

Chemical Properties

Tβ4 is a water‐soluble G‐actin–sequestering protein with a molecular weight of 4.9 kDa and a pI of 5.1. Tβ4 comprises 43 amino acid residues, the most abundant of which are glutamate and glycine. Protein conformation analysis has shown that there is a high helical content at positions 4‐15 and 30‐40 of the amino acid sequence of Tβ4. Additionally, internal overlap is observed at positions 18‐30 and 31‐43. N‐acetyl‐seryl‐aspartyl‐lysyl‐proline is the N‐terminal amino acid residue sequence of Tβ4, which can be obtained by direct cleavage of the chemical bond between proline and aspartic acid using prolyl oligopeptidase or Aspn‐like protease. Nuclear magnetic resonance analysis showed that Tβ4 mainly contains α helices in aqueous solution, exhibiting a loose structure. When the pH value of the aqueous solution is 4.5‐7.5, and the temperature is between 5 and 40°C, the secondary structure of Tβ4 is difficult to identify. In addition to its binding affinity to G‐actin, Tβ4 can form complexes with F‐actin[1].

benefits

Thymosin Beta-4 is a 43-amino-acid peptide that promotes healing throughout the body. It also has anti-inflammatory properties. Found naturally in higher concentrations at injury sites, the water-soluble protein can repair tissue damage and regulate cell migration to a site. It can improve wound healing and repair not only the skin, but also the brain, spinal cord, and heart. Medical professionals consider Thymosin Beta-4 a safe and powerful substance in its natural or synthetic form known as TB-500.
In addition, TB4 has a low molecular weight and doesn’t bind to the extracellular matrix. This enables it to easily travel throughout body tissues, which promotes a faster rate of healing. The peptide travels long distances, so it usually doesn’t have to be injected directly at the injury site. While some believe injecting it closer to an injured area yields better results, clinical evidence suggests otherwise.

Mechanism of action

Recent studies have revealed that the first gene to be upregulated after an injury is a Thymosin beta 4 gene. As the body begins the recovery process,Thymosin beta 4 aids in the creation of new vessels in the injured area, which carry blood, nutrients, and reparative substances to the site. It also has anti-inflammatory properties and works to decrease the amount of inflammatory substances, called cytokines. Inflammation plays a large role in many of the symptoms associated with a number of other conditions (i.e., Lyme disease, CFS, FM, autoimmune diseases, infections, etc.), making the potential impact of Tβ4 quite extensive.

Biological Activity

Thymosin beta 4 (Tβ4) is a highly conserved G‐actin–sequestering protein that is involved in various biological processes, such as cell migration, angiogenesis and wound healing. Recently, Tβ4 has been shown to play critical roles in hair follicle (HF) growth and development. Moreover, endogenous Tβ4 can activate the HF cycle transition in mice and affect HF growth and development by promoting the migration and differentiation of HF stem cells and their progeny. In addition, exogenous Tβ4 increases the rate of hair growth in mice and promotes cashmere production by increasing the number of secondary HFs in cashmere goats[1].

Clinical Use

Thymosin beta 4 has been used in the treatment of HIV, AIDS, Influenza, colds, and various infections. It has been utilized in the management of various inflammatory conditions, as well as part of treatment following a heart attack due to its cardio and neuroprotective effects.

Side effects

Many studies have found that Thymosin beta 4 is a safely consumable peptide. The main side effect of Thymosin beta 4 is related to its anti-apoptotic activity, as it may promote the metastatic potential of tumor cells and enable rapid spread. Additionally, common mild side effects of this peptide include redness and discomfort at joints, and in some cases, it may even cause tiredness, lethargy, and headaches.

References

[1] Bai Dai. “Multiple potential roles of thymosin β4 in the growth and development of hair follicles.” JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 25 3 (2021): 1350–1358.