Cellular proteostasis: a new twist in the action of thymosin α1

Claudia Stincardini, Giorgia Renga, Valeria Villella, Marilena Pariano, Vasilis Oikonomou, Monica Borghi, Marina M Bellet, Luigi Sforna, Claudio Costantini, Allan L Goldstein, Enrico Garaci, Luigina Romani

Research output: Contribution to journalReview article

Abstract

INTRODUCTION: Thymosin alpha 1 (Tα1) is a naturally occurring polypeptide of 28 amino acids, whose mechanism of action is thought to be related to its ability to signal through innate immune receptors. Tα1 (ZADAXIN®) is used worldwide for treating viral infections, immunodeficiencies, and malignancies. Owing to its ability to activate the tolerogenic pathway of tryptophan catabolism - via the immunoregulatory enzyme indoleamine 2,3-dioxygenase - Tα1 potentiates immune tolerance mechanisms, breaking the vicious circle that perpetuates chronic inflammation in response to a variety of infectious noxae. Areas covered: Tα1 has never been studied in Cystic fibrosis (CF) in which the hyperinflammatory state is associated with early and nonresolving activation of innate immunity, which impairs microbial clearance and promotes a self-sustaining condition of progressive lung damage. Optimal CF treatments should, indeed, not only rescue CF transmembrane conductance regulator protein localization and functionality but also alleviate the associated hyperinflammatory pathology. Because of the inherent complexity of the pathogenetic mechanisms, a multidrug approach is required. Expert opinion: By providing a multipronged attack against CF, i.e. restraining inflammation and correcting the basic defect, Tα1 favorably opposed CF symptomatology in preclinical relevant disease settings, thus suggesting its possible exploitation for 'real-life' clinical efficacy in CF. This could represent a major conceptual advance in the CF field, namely the proposal of a drug with the unique activity to correct CFTR defects through regulation of inflammation.

Original languageEnglish
Pages (from-to)43-48
Number of pages6
JournalExpert Opinion on Biological Therapy
Volume18
Issue numbersup1
DOIs
Publication statusPublished - Jul 2018

Fingerprint

Thymosin
Cystic Fibrosis
Inflammation
Noxae
Indoleamine-Pyrrole 2,3,-Dioxygenase
Cystic Fibrosis Transmembrane Conductance Regulator
Defects
Pathology
Immune Tolerance
Tryptophan
Expert Testimony
Virus Diseases
Innate Immunity
Chemical activation
thymalfasin
Amino Acids
Peptides
Enzymes
Lung
Pharmaceutical Preparations

Keywords

  • Animals
  • Cystic Fibrosis Transmembrane Conductance Regulator/physiology
  • Humans
  • Immune Tolerance/drug effects
  • Immunity, Innate/drug effects
  • Inflammation/genetics
  • Proteostasis/drug effects
  • Signal Transduction/drug effects
  • Thymalfasin/pharmacology

Cite this

Stincardini, C., Renga, G., Villella, V., Pariano, M., Oikonomou, V., Borghi, M., ... Romani, L. (2018). Cellular proteostasis: a new twist in the action of thymosin α1. Expert Opinion on Biological Therapy, 18(sup1), 43-48. https://doi.org/10.1080/14712598.2018.1484103

Cellular proteostasis : a new twist in the action of thymosin α1. / Stincardini, Claudia; Renga, Giorgia; Villella, Valeria; Pariano, Marilena; Oikonomou, Vasilis; Borghi, Monica; Bellet, Marina M; Sforna, Luigi; Costantini, Claudio; Goldstein, Allan L; Garaci, Enrico; Romani, Luigina.

In: Expert Opinion on Biological Therapy, Vol. 18, No. sup1, 07.2018, p. 43-48.

Research output: Contribution to journalReview article

Stincardini, C, Renga, G, Villella, V, Pariano, M, Oikonomou, V, Borghi, M, Bellet, MM, Sforna, L, Costantini, C, Goldstein, AL, Garaci, E & Romani, L 2018, 'Cellular proteostasis: a new twist in the action of thymosin α1', Expert Opinion on Biological Therapy, vol. 18, no. sup1, pp. 43-48. https://doi.org/10.1080/14712598.2018.1484103
Stincardini C, Renga G, Villella V, Pariano M, Oikonomou V, Borghi M et al. Cellular proteostasis: a new twist in the action of thymosin α1. Expert Opinion on Biological Therapy. 2018 Jul;18(sup1):43-48. https://doi.org/10.1080/14712598.2018.1484103
Stincardini, Claudia ; Renga, Giorgia ; Villella, Valeria ; Pariano, Marilena ; Oikonomou, Vasilis ; Borghi, Monica ; Bellet, Marina M ; Sforna, Luigi ; Costantini, Claudio ; Goldstein, Allan L ; Garaci, Enrico ; Romani, Luigina. / Cellular proteostasis : a new twist in the action of thymosin α1. In: Expert Opinion on Biological Therapy. 2018 ; Vol. 18, No. sup1. pp. 43-48.
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AU - Pariano, Marilena

AU - Oikonomou, Vasilis

AU - Borghi, Monica

AU - Bellet, Marina M

AU - Sforna, Luigi

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AU - Goldstein, Allan L

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N2 - INTRODUCTION: Thymosin alpha 1 (Tα1) is a naturally occurring polypeptide of 28 amino acids, whose mechanism of action is thought to be related to its ability to signal through innate immune receptors. Tα1 (ZADAXIN®) is used worldwide for treating viral infections, immunodeficiencies, and malignancies. Owing to its ability to activate the tolerogenic pathway of tryptophan catabolism - via the immunoregulatory enzyme indoleamine 2,3-dioxygenase - Tα1 potentiates immune tolerance mechanisms, breaking the vicious circle that perpetuates chronic inflammation in response to a variety of infectious noxae. Areas covered: Tα1 has never been studied in Cystic fibrosis (CF) in which the hyperinflammatory state is associated with early and nonresolving activation of innate immunity, which impairs microbial clearance and promotes a self-sustaining condition of progressive lung damage. Optimal CF treatments should, indeed, not only rescue CF transmembrane conductance regulator protein localization and functionality but also alleviate the associated hyperinflammatory pathology. Because of the inherent complexity of the pathogenetic mechanisms, a multidrug approach is required. Expert opinion: By providing a multipronged attack against CF, i.e. restraining inflammation and correcting the basic defect, Tα1 favorably opposed CF symptomatology in preclinical relevant disease settings, thus suggesting its possible exploitation for 'real-life' clinical efficacy in CF. This could represent a major conceptual advance in the CF field, namely the proposal of a drug with the unique activity to correct CFTR defects through regulation of inflammation.

AB - INTRODUCTION: Thymosin alpha 1 (Tα1) is a naturally occurring polypeptide of 28 amino acids, whose mechanism of action is thought to be related to its ability to signal through innate immune receptors. Tα1 (ZADAXIN®) is used worldwide for treating viral infections, immunodeficiencies, and malignancies. Owing to its ability to activate the tolerogenic pathway of tryptophan catabolism - via the immunoregulatory enzyme indoleamine 2,3-dioxygenase - Tα1 potentiates immune tolerance mechanisms, breaking the vicious circle that perpetuates chronic inflammation in response to a variety of infectious noxae. Areas covered: Tα1 has never been studied in Cystic fibrosis (CF) in which the hyperinflammatory state is associated with early and nonresolving activation of innate immunity, which impairs microbial clearance and promotes a self-sustaining condition of progressive lung damage. Optimal CF treatments should, indeed, not only rescue CF transmembrane conductance regulator protein localization and functionality but also alleviate the associated hyperinflammatory pathology. Because of the inherent complexity of the pathogenetic mechanisms, a multidrug approach is required. Expert opinion: By providing a multipronged attack against CF, i.e. restraining inflammation and correcting the basic defect, Tα1 favorably opposed CF symptomatology in preclinical relevant disease settings, thus suggesting its possible exploitation for 'real-life' clinical efficacy in CF. This could represent a major conceptual advance in the CF field, namely the proposal of a drug with the unique activity to correct CFTR defects through regulation of inflammation.

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KW - Signal Transduction/drug effects

KW - Thymalfasin/pharmacology

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JO - Expert Opinion on Biological Therapy

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