a Journal of Postdoctoral Research and Postdoctoral Affairs.
    ISSN : 2328-9791
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The role of Glucocerebrosidase GBA2 in cystic fibrosis lung inflammation: from molecular mechanism to therapeutic strategies
Author(s) : Aureli M, Loberto N, Bassi R, Schiumarini D, Munari S, Valsecchi M, Cantù L, Brocca P, Motta S, Ferrami G, Dechecchi C, Sonnino S
Address : Department of Medical Biochemistry and Translational Medicine, University of Milano, Laboratory of Molecular Pathology-Azienda Ospedaliera Universitaria Integrata di Verona, Italy
University of Milano; Universitaria Integrata di Verona.

Background. Several studies indicate that sphingolipids (SL) play a regulatory role in airway inflammation, the most critical aspect of CF lung disease. Recently, Ceramide (Cer) derived from glycosphingolipids (GSL) has gained more interest since inhibition of the glucocerebrosidase GBA2 and its down-regulation by siRNA, are associated with a significant reduction of IL-8 after P.aeruginosa (PAO) infection, as well as a reduction of the intrinsic inflammatory state in CF human epithelial bronchial cells (CFhEBC).

Hypothesis and Objectives. In our work hypothesis, the aberrant inflammatory response to PAO in CFhEBC starts from alterations in the lipid composition of specific plasma membrane (PM) macromolecular complex by the action of the GSL-hydrolases associated with the cell surface, including GBA2. To figure out the possible molecular mechanism we investigated the effect of PAO infection on specialized membrane area called lipids rafts. Moreover, with the aim to develop a new anti-inflammatory treatment we developed new lipid based-nanoparticles for the delivery of siRNA targeting GBA2.


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