Peptide-based molecules for αvβ3 integrin modulation in Th17 cells-dependent demyelinating diseases
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Peptide-based molecules for αvβ3 integrin modulation in Th17 cells-dependent demyelinating diseases
Research areas: Small molecules and peptides/modified peptides for diagnostic, therapeutic and biotechnological applications, 

Keywords: Design, synthesis, peptide inhibitors/antagonists, integrins, demyelinating disease, CNS inflammation, Th17 cells.

Contact person: Laura Zaccaro, lzaccarounina.it

Actors: Annarita Del Gatto, annarita.delgattocnr.it, Laura Zaccaro, lzaccarounina.it,

Description:
Inerleukin-23 (IL-23) is required for inflammatory Th17 cell function in experimental model of demyelinating disease (Experimental Autoimmune Encephalomyelitis EAE), and IL-23 blockade reduces the number of effector Th17 cells in the CNS. It has been reported that Th17 cells express high integrin β3 that is IL-23 dependent. Integrin β3 is not upregulated on all activated T cells; rather, it is upregulated along with its functional partner integrin αv on effector Th17 cells. Integrin αvβ3 inhibitors ameliorate clinical signs of EAE and integrin-β3-deficient Th17 cells, but not Th1 cells, are impaired in their ability to induce EAE. Hence, integrin β3 is required for Th17 cell-mediated autoimmune CNS inflammation.

Currently, many treatments for demyelinating diseases include injectable drugs that are not specific but suppress the general immune response leading to many negative side effects; thus, the development of therapeutic agents able to specifically control and modulate Th17 cells activity, pivotal players in the CNS inflammation, is an urgent need.

Our group has gained experience in the design, synthesis, structural and biological characterization of new peptide-based molecules selective for different type of integrins. To this regard, our aim is to develop αvβ3 integrin antagonists able to selectively modulate the receptor activity in EAE and with high enzymatic stability for obtaining orally administrated drugs. Thanks to the collaboration with Prof. Mandy J. McGeachy from University of Pittsburghthe ability of the peptides in the modulation of Th17 function in EAE model is investigated.

Selected papers:

-  Du, F. et al. Inflammatory Th17 Cells Express Integrin αvβ3 for Pathogenic Function. Cell Reports 2016, 16, 1339. doi:10.1016/j.celrep.2016.06.065

-   Comegna, D. et al. Chemical Modification for Proteolytic Stabilization of the Selective alpha(v)beta(3) Integrin RGDechi Peptide: in Vitro and in Vivo Activities on Malignant Melanoma Cells. J Med Chemv 2017, 60, 9874. doi: 10.1021/acs.jmedchem.7b01590

-  Del Gatto, A. et al. Novel and selective alpha(v)beta(3) receptor peptide antagonist: Design, synthesis, and biological behavior. J Med Chem 2006, 49, 3416. doi: 10.1021/jm060233m

Peptide-based molecules for αvβ3 integrin modulation in Th17 cells-dependent demyelinating diseases
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Peptide-based molecules for αvβ3 integrin modulation in Th17 cells-dependent demyelinating diseases
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Last modified by Marco Comerci on Monday 30 November 2020, 17:28:06
152 views. Last view on Saturday 01 June 2024, 14:01:21