Thymosin Beta-4 (Tβ4) is a naturally occurring 43-amino acid peptide found in virtually all human cells except red blood cells. It is the primary G-actin sequestering peptide in the body and plays crucial roles in tissue repair, regeneration, and protection from injury.
Structure
Tβ4 consists of 43 amino acids with the sequence: Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES
The N-terminus is acetylated, and the peptide has a molecular weight of approximately 4,921 Da. It is highly water-soluble with an isoelectric point of 5.1.
Mechanism of Action
Actin Binding
Tβ4 sequesters G-actin monomers, regulating the actin cytoskeleton essential for cell migration, division, and morphology. This action is fundamental to wound healing and tissue repair.
Regenerative Signaling
After injury, Tβ4 is released by platelets, macrophages, and other cell types to:
- Protect cells from further damage and reduce apoptosis
- Decrease inflammation and microbial growth
- Promote migration of stem/progenitor cells
- Stimulate angiogenesis (new blood vessel formation)
- Support tissue regeneration
Cardioprotective Effects
Tβ4 is the first known molecule able to initiate simultaneous myocardial and vascular regeneration after systemic administration. It activates endogenous cardiac progenitors by reactivating embryonic developmental programs.
Research Applications
- Wound Healing: Promotes full-thickness cutaneous wound healing and reduces scar formation
- Cardiac Repair: Inhibits myocardial cell death, stimulates vessel growth post-MI
- Corneal Healing: Phase 2/3 trials for ophthalmic applications
- Neuroprotection: Benefits following stroke and TBI
Relationship to TB-500
TB-500 is a synthetic fragment of Thymosin Beta-4, containing the 17-amino acid active region. The full Tβ4 molecule contains additional sequences that may provide distinct biological activities.
Current Status
Tβ4 is under investigation in clinical trials for cardiac repair, corneal injuries, and wound healing. It is currently classified as a research compound and is not FDA-approved.