Thymosin α1 explained

Thymosin α₁ is a peptide fragment derived from prothymosin alpha, a protein that in humans is encoded by the PTMA gene.^[1]

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.^[2]

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 has been found to enhance cell-mediated immunity in humans as well as experimental animals.^[3]

Therapeutic application

Thymosin α₁ is 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.^{[4] [5]}

Clinical studies

Clinical trials suggest it may be useful in cystic fibrosis, septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients.,^[5] and for chronic hepatitis B.^[6]

It has been studied for possible use in treating cancer (e.g. with chemotherapy).^[7]

See also

• Thymosins

Further reading

• Martini PG, Katzenellenbogen BS . Modulation of estrogen receptor activity by selective coregulators. . J. Steroid Biochem. Mol. Biol. . 85 . 2–5 . 117–22 . 2003 . 12943695 . 10.1016/S0960-0760(03)00207-3 . 32374864 .
• Barcia MG, Castro JM, Jullien CD, etal . Prothymosin alpha is phosphorylated by casein kinase-2. . FEBS Lett. . 312 . 2–3 . 152–6 . 1992 . 1426245 . 10.1016/0014-5793(92)80924-6 . 84760219 . free .
• Baxevanis CN, Thanos D, Reclos GJ, etal . Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. . J. Immunol. . 148 . 7 . 1979–84 . 1992 . 10.4049/jimmunol.148.7.1979 . 1545115 . 36407216 . free .
• Gallego R, Rosón E, García-Caballero T, etal . Prothymosin alpha expression in lymph nodes and tonsils: an optical and ultrastructural study. . Acta Anat (Basel) . 143 . 3 . 219–22 . 1992 . 1632187 . 10.1159/000147251 .
• Cordero OJ, Sarandeses CS, López JL, etal . Prothymosin alpha enhances interleukin 2 receptor expression in normal human T-lymphocytes. . Int. J. Immunopharmacol. . 13 . 8 . 1059–65 . 1992 . 1814846 . 10.1016/0192-0561(91)90156-2 .
• Watts JD, Cary PD, Sautiere P, Crane-Robinson C . Thymosins: both nuclear and cytoplasmic proteins. . Eur. J. Biochem. . 192 . 3 . 643–51 . 1990 . 2209614 . 10.1111/j.1432-1033.1990.tb19271.x . free .
• Eschenfeldt WH, Manrow RE, Krug MS, Berger SL . Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products. . J. Biol. Chem. . 264 . 13 . 7546–55 . 1989 . 10.1016/S0021-9258(18)83269-0 . 2708378 . free .
• Gómez-Márquez J, Segade F, Dosil M, etal . The expression of prothymosin alpha gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation. . J. Biol. Chem. . 264 . 15 . 8451–4 . 1989 . 10.1016/S0021-9258(18)81807-5 . 2785990 . free .
• Goodall GJ, Dominguez F, Horecker BL . Molecular cloning of cDNA for human prothymosin alpha. . Proc. Natl. Acad. Sci. U.S.A. . 83 . 23 . 8926–8 . 1987 . 3466166 . 10.1073/pnas.83.23.8926 . 387046 . free .
• Eschenfeldt WH, Berger SL . The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA. . Proc. Natl. Acad. Sci. U.S.A. . 83 . 24 . 9403–7 . 1987 . 3467312 . 10.1073/pnas.83.24.9403 . 387146 . free .
• Panneerselvam C, Haritos AA, Caldarella J, Horecker BL . Prothymosin alpha in human blood. . Proc. Natl. Acad. Sci. U.S.A. . 84 . 13 . 4465–9 . 1987 . 3474615 . 10.1073/pnas.84.13.4465 . 305110 . 1987PNAS...84.4465P . free .
• Pan LX, Haritos AA, Wideman J, etal . Human prothymosin alpha: amino acid sequence and immunologic properties. . Arch. Biochem. Biophys. . 250 . 1 . 197–201 . 1986 . 3532956 . 10.1016/0003-9861(86)90717-4 .
• Kubota S, Adachi Y, Copeland TD, Oroszlan S . Binding of human prothymosin alpha to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev. . Eur. J. Biochem. . 233 . 1 . 48–54 . 1995 . 7588773 . 10.1111/j.1432-1033.1995.048_1.x . free .
• Garcia-Caballero T, Dominguez F, Roson E, etal . Distribution of prothymosin alpha in rat and human adrenal cortex. . Anat. Rec. . 239 . 1 . 88–94 . 1994 . 7913591 . 10.1002/ar.1092390110 . 38666222 .
• Szabo P, Panneerselvam C, Clinton M, etal . Prothymosin alpha gene in humans: organization of its promoter region and localization to chromosome 2. . Hum. Genet. . 90 . 6 . 629–34 . 1993 . 7916742 . 10.1007/BF00202480 . 6902846 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Tsitsiloni OE, Stiakakis J, Koutselinis A, etal . Expression of alpha-thymosins in human tissues in normal and abnormal growth. . Proc. Natl. Acad. Sci. U.S.A. . 90 . 20 . 9504–7 . 1993 . 8415730 . 10.1073/pnas.90.20.9504 . 47597 . 1993PNAS...90.9504T . free .
• Sburlati AR, De La Rosa A, Batey DW, etal . Phosphorylation of human and bovine prothymosin alpha in vivo. . Biochemistry . 32 . 17 . 4587–96 . 1993 . 8485135 . 10.1021/bi00068a015 .
• Rubtsov IuP . Vartapetian AB . [New intronless members of human prothymosin alpha genes] . Mol. Biol. (Mosk.) . 29 . 6 . 1320–5 . 1996 . 8592501 .

Notes and References

1. Manrow RE, Leone A, Krug MS, Eschenfeldt WH, Berger SL . The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions . Genomics . 13 . 2 . 319–31 . Jul 1992 . 1612591 . 10.1016/0888-7543(92)90248-Q .
2. Garaci E . Thymosin alpha1: a historical overview . Ann. N. Y. Acad. Sci. . 1112 . 14–20 . September 2007 . 17567941 . 10.1196/annals.1415.039 . 222082988 .
3. Wara DW, Goldstein AL, Doyle NE, Ammann AJ . Thymosin activity in patients with cellular immunodeficiency . N. Engl. J. Med. . 292 . 2 . 70–4 . January 1975 . 1078552 . 10.1056/NEJM197501092920204.
4. Garaci E, Favalli C, Pica F, etal . Thymosin alpha 1: from bench to bedside . Ann. N. Y. Acad. Sci. . 1112 . 225–34 . September 2007 . 1 . 17600290 . 10.1196/annals.1415.044 . 2007NYASA1112..225G . 28283520 .
5. Goldstein AL, Goldstein AL . From lab to bedside: emerging clinical applications of thymosin alpha 1 . Expert Opin Biol Ther . 9 . 5 . 593–608 . May 2009 . 19392576 . 10.1517/14712590902911412 . 71893579 .
6. 10.1517/14712598.2015.1007948 . 15 . Thymosin alpha-1 treatment in chronic hepatitis B . 2015 . Expert Opinion on Biological Therapy . 129–132 . Wu X, Jia J, You H. 25640173 . 41148652 .
7. 11137613 . 22 . Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application . 2000 . Int J Immunopharmacol . 1067–76 . Garaci E, Pica F, Rasi G, Favalli C. 12 . 10.1016/s0192-0561(00)00075-8 .