Precortistatin is a protein that in humans is encoded by the CORT gene. The 105 amino acid residue human precortistatin in turn is cleaved into cortistatin-17 and cortistatin-29. Cortistatin-17 is the only active peptide derived from the precursor.
Another study tested Cortistatin to treat Osteoarthritis on mice. Osteoarthritis is a degenerative joint disease caused by the breakdown of cartilage. The tumor necrosis factor (TNF-α) is known to play a critical role in Osteoarthritis. The results showed that Cortistatin competitively bounded to TNFR1 as well as TNFR2. Cortistatin suppressed the proinflammatory function of TNF-α. Notably, both the spontaneous and surgically induced Osteoarthritis models indicated that deficiency of Cortistatin led to an accelerated Osteoarthritis-like phenotype. Analysis of TNFR1- and TNFR2-knockout mice found that TNFRs might be involved in the protective role of Cortistatin in Osteoarthritis. Mice treated with cortistatin for 3 consecutive days starting 6 days after TNBS administration and the onset of disease quickly reversed the lost body weight. Cortistatin treatment completely removed established colitis and reduced the disease recurrence. Mice treated with cortistatin 12 h after TNBS injection survived and did not suffer disease recurrence after a second administration of TNBS.
Another study tested Cortistatin treatments on a preclinical mouse model of Parkinson’s disease induced by acute exposure to the neurotoxin 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine (MPTP). Researchers observed that treatment with cortistatin mitigated the MPTP-induced loss of dopaminergic neurons, which are in the substantia nigra and their connections to the striatum. The study found that cortistatin administration improved the locomotor activity of mice intoxicated with 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine. The study also found that cortistatin diminished the presence and activation of glial cells in the affected brain regions of 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine-treated mice. Cortistatin also reduced the production of immune mediators and also promoted the expression of neurotrophic factors in the striatum of mice. In conclusion, these findings again suggest that cortistatin could emerge as a potential antiinflammatory factor and that cortistatin has neuroprotective properties to regulate the progression of Parkinson’s disease.
The 14mer cortistatin and somatostatin peptides are similar in structure, with the rat peptides sharing 11 of their 14 residues. Most of their structural differences lie outside of the cyclic portion of the peptide. In the N-terminal, extra-cyclic residues in CST14 are a Pro for rat and ouse or Asp-Arg-Met-Pro for human and in SST14, there is an Ala-Gly pair in this position. The C-terminal portion of SST14 ends in the amino acid Cys that forms the part of the Cys–Cys loop, whereas an amino acid Lys residue is predicted to be C-terminal of this Cys for all of the known CST14 peptides. However it was not clear if this extracyclic C-terminal CST14 Lys residue is present in a mature peptide because it represents an attractive site for proteolysis by the carboxypeptidase enzymes. Although radio-immunoassay of the HPLC fractions of brain extracts identifies a peptide with a more identical elution profile to CST14 Inside the Cys–Cys loop, for rat and mouse CST14 peptides are identical in sequence, with the human form containing one difference. The difference is that in the human form, Arg follows the N-terminal Cys residue, which is a Lys in the other CST14 peptides. The Cys–Cys loop of CST14 peptides is different from the SST14 peptides because of a Ser residue present two positions N-terminal of the C-terminal Cys, which is a Thr residue in SST14. With that said, a notable number of these structural differences have been shown to have physiological and pharmacological significance for Protein Cortistatin .
Synthesis
Synthesis of Cortistatin
For Synthesis of Cortistatin is was speculated that cortistatins A and J may derive from cortistatin L or a precursor of the same oxidation state, and Cortistatin L might in turn be derived by C2 oxidation of cortistatin K. Cortistatins A, J, K, and L have been synthesized in parallel processes from like intermediates prepared from a single compound. The cortistatins Synthesis are an identified class of marine natural products characterized by an unusual steroidal skeleton. The unusual steroidal skeleton has been found to be able to inhibit the proliferation of various mammalian cells in culture by an unknown mechanism.