Thymosins

Thymosins are small proteins present in many animal tissues. They are named thymosins because they were originally isolated from the thymus, but most are now known to be present in many other tissues. Thymosins have diverse biological activities, and two in particular, thymosins α₁ and β₄, have potentially important uses in medicine, some of which have already progressed from the laboratory to the clinic. In relation to diseases, thymosins have been categorized as biological response modifiers.

Discovery

The discovery of thymosins in the mid 1960s emerged from investigations of the role of the thymus in development of the vertebrate immune system. Begun by Allan Goldstein in the Laboratory of Abraham White at the Albert Einstein College of Medicine in New York, the work continued at University of Texas Medical Branch in Galveston and at The George Washington University School of Medicine and Health Sciences in Washington D.C. The supposition that the role of the thymus might involve a hormone-like mechanism led to the isolation from thymus tissue of a biologically active preparation. Known as "Thymosin Fraction 5", this was able to restore some aspects of immune function in animals lacking thymus gland. Fraction 5 was found to contain over 40 small peptides (molecular weights ranging from 1000 to 15,000 Da.), which were named "thymosins" and classified as α, β and γ thymosins on the basis of their behaviour in an electric field. Although found together in Fraction 5, they are now known to be structurally and genetically unrelated. Thymosin β₁ was found to be ubiquitin (truncated by two C-terminal glycine residues).

Thymosin beta-4

Thymosin beta-4 is a protein that in humans is encoded by the TMSB4X gene.

The protein consists (in humans) of 43 amino acids (msdkpdmaei ekfdksklkk tetqeknplp sketieqekq ages) molWt 4921.

Function

This gene encodes an actin sequestering protein which plays a role in regulation of actin polymerization. The protein is also involved in cell proliferation, migration, and differentiation. This gene escapes X inactivation and has a homolog on chromosome Y (TMSB4Y).

Clinical significance

It has been studied in a number of clinical trials.

The thymosin beta-4 peptide, if used after a heart attack, might reactivate cardiac progenitor cells to repair damaged heart tissue.

Doping in Sports

Thymosin beta-4 was allegedly used by some players in various Australian football codes and is under investigation by the Australian Sports Anti-Doping Authority for anti-doping violations

Players of the Essendon Football Club were cleared of use of Thymosin Beta 4 on March 30, 2015 by the Australian Football League anti-doping tribunal, however after an appeal by the World Anti-Doping Agency, this was overturned on the January 12, 2016.

Thymosin α1

Thymosin α₁ is a peptide fragment derived from prothymosin alpha, a protein that in humans is encoded by the PTMA gene.

Function

Thymosin α₁ is believed to be a major component of Thymosin Fraction 5 responsible for the activity of that preparation in restoring immune function in animals lacking thymus glands. It was the first of the peptides from Thymosin Fraction 5 to be completely sequenced and synthesized. Unlike β thymosins, to which it is genetically and chemically unrelated, thymosin α₁ is produced as a 28-amino acid fragment, from a longer, 113-amino acid precursor, prothymosin α. It has been found to enhance cell-mediated immunity in humans as well as experimental animals.

Therapeutic application

Thymosin α₁ is now approved in 35 under developed or developing countries for the treatment of Hepatitis B and C, and it is also used to boost the immune response in the treatment of other diseases.

See also

References

Further reading