Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application

Severa, Martina; Zhang, Jing; Giacomini, Elena; Rizzo, Fabiana; Etna, Marilena P.; Cruciani, Melania; Garaci, Enrico; Chopp, Michael; Coccia, Eliana M.

doi:10.1016/j.msard.2018.09.035

Cited by 22 publications

(23 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, Tα1 was shown to prevent intestinal toxicity in a murine model of anti-CTLA-4-induced colitis, hence contributing to an improved safety profile of immune checkpoint inhibitors [ 17 ]. Beyond that, emerging indications such as cystic fibrosis [ 18 ], multiple sclerosis [ 19 ], and sepsis [ 20 ] further emphasize the huge potential of this small therapeutic peptide. Finally, with the outbreak of the COVID-19 pandemic, Tα1 recently gained new attention in virology.…”

Section: Introductionmentioning

confidence: 99%

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology

Binder¹,

Skerra

2020

IJMS

View full text Add to dashboard Cite

Thymosin α1 (Tα1) is an immunostimulatory peptide for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and used as an immune enhancer, which also offers prospects in the context of COVID-19 infections and cancer. Manufacturing of this N-terminally acetylated 28-residue peptide is demanding, and its short plasma half-life limits in vivo efficacy and requires frequent dosing. Here, we combined the PASylation technology with enzymatic in situ N-acetylation by RimJ to produce a long-acting version of Tα1 in Escherichia coli at high yield. ESI-MS analysis of the purified fusion protein indicated the expected composition without any signs of proteolysis. SEC analysis revealed a 10-fold expanded hydrodynamic volume resulting from the fusion with a conformationally disordered Pro/Ala/Ser (PAS) polypeptide of 600 residues. This size effect led to a plasma half-life in rats extended by more than a factor 8 compared to the original synthetic peptide due to retarded kidney filtration. Our study provides the basis for therapeutic development of a next generation thymosin α1 with prolonged circulation. Generally, the strategy of producing an N-terminally protected PASylated peptide solves three major problems of peptide drugs: (i) instability in the expression host, (ii) rapid degradation by serum exopeptidases, and (iii) low bioactivity because of fast renal clearance.

show abstract

Section: Introductionmentioning

confidence: 99%

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology

Binder¹,

Skerra

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Thymosin, soluble hormone-like peptides produced by the thymus gland, can mediate immune and non-immune physiological processes and have gained interest in recent years as therapeutics in inflammatory and autoimmune diseases (Severa et al, 2019). Thymalin and thymosin are the main components of thymus extract.…”

mentioning

confidence: 99%

Immuno Protective, Anti-Diabetic and Histochmical-Anti Oxidative Activities of L-Carnitine, and Calf Thymus Extract in Aged Male Mice.

El-Gendy¹,

Rmasoud²,

SHadad³

et al. 2019

IJAR

View full text Add to dashboard Cite

Immuno-protective, Anti-diabietic and Histochmical antioxidantive effect, Lcarnitine and calf thymus extract. Background: The mechanisms behind of immunosenescence have remained largely unknown in elderly. Some studies are referred the cause to that, L-carnitine is essential nutrient factor which it is important in transporting of long chain fatty acids to mitochondrial matrix, a process essential for fatty acid oxidation and energy release. The immunobiological properties of a new formulation of the lipid thymus calf extract (CYTOIMMUNE ®) were determined. Methods: In this study, the immunomodulating effect of L-carnitine and calf thymus extract were studied in aged male mice. Forty mice were divided into four groups, each group included ten aged male mice. Group I, each mice was injected intraperitoneal (I.P.) with normal saline for 7 successive days. Group II, each mice was injected I.P. with L-carnitine at dose 200 mg/kg b.wt. for 7 successive days. Group III, each mice was injected I.P. with calf thymus extract at dose 0.5 mg/kg b.wt. for 7 successive days. Group IV, each mice was injected I.P. with L-carnitine at dose 200 mg/kg b.wt. Plus calf thymus extract at dose 0.5 mg/kg b.wt. for 7 successive days. RBCs & WBCs count, PCV, differential leukocytic count, phagocytic activity, phagocytic index, total protein, globulin, albumin, interleukin2, ALT, AST & blood glucose were measured. Moreover, after slaughtering the animals , histological sections were taken from main internal organs (liver, spleen, kidney) to show internal changes of previous tissues and evaluated the protective and antioxidant properties by using the previous experimental preparations (L-carnitine at dose 200 mg/kgb.wt. , calf thymus extract at dose 0.5 mg/kg b.wt. and combination of them). Results: The interaperiotoneal administration of L-carnitine at dose 200 mg/kg b.wt. calf thymus extract at dose 0.5 mg/kg b.wt. and combination between them. L-carnitine at dose 200 mg/kg b.wt.and calf thymus extract at dose 0.5 mg/kg b.wt. for 7 successive days had an improving effect on immune response, glucose level and hepatic marker enzymes as well as improving the histological architecture in the internal tissues (liver, kidney and spleen) and a significant increase in CAT (catalase enzyme), in liver and kidney. These results clearly

show abstract

“…Progress in purification procedures allowed to discriminate numerous functionally different peptides, part of which belong to the more generally known thymosin fractions-3 and -5 [ 92 ]. According to isoelectric focusing patterns, three groups were distinguished, α-, β-, and γ-thymosins, with IEPs respectively, below pH 5, between pH 5 and 7, and above pH 7, which remained to be highly heterogeneous [ 93 ]. Thymosin fraction-5 (TF5) alone contains over 40 different molecules [ 94 ].…”

Section: Revisiting the Thymus Glandmentioning

confidence: 99%

Thymus-Pineal Gland Axis: Revisiting Its Role in Human Life and Ageing

Rezzani

Franco

Hardeland

et al. 2020

IJMS

View full text Add to dashboard Cite

For years the thymus gland (TG) and the pineal gland (PG) have been subject of increasingly in-depth studies, but only recently a link that can associate the activities of the two organs has been identified. Considering, on the one hand, the well-known immune activity of thymus and, on the other, the increasingly emerging immunological roles of circadian oscillators and the rhythmically secreted main pineal product, melatonin, many studies aimed to analyse the possible existence of an interaction between these two systems. Moreover, data confirmed that the immune system is functionally associated with the nervous and endocrine systems determining an integrated dynamic network. In addition, recent researches showed a similar, characteristic involution process both in TG and PG. Since the second half of the 20th century, evidence led to the definition of an effectively interacting thymus-pineal axis (TG-PG axis), but much has to be done. In this sense, the aim of this review is to summarize what is actually known about this topic, focusing on the impact of the TG-PG axis on human life and ageing. We would like to give more emphasis to the implications of this dynamical interaction in a possible therapeutic strategy for human health. Moreover, we focused on all the products of TG and PG in order to collect what is known about the role of peptides other than melatonin. The results available today are often unclear and not linear. These peptides have not been well studied and defined over the years. In this review we hope to awake the interest of the scientific community in them and in their future pharmacological applications.

show abstract

Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application

Cited by 22 publications

References 114 publications

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology

Immuno Protective, Anti-Diabetic and Histochmical-Anti Oxidative Activities of L-Carnitine, and Calf Thymus Extract in Aged Male Mice.

Thymus-Pineal Gland Axis: Revisiting Its Role in Human Life and Ageing

Contact Info

Product

Resources

About