Calcineurin Inhibitor Market growth is projected to reach USD 13.82 Billion, at a 3.32% CAGR by driving industry size, share, top company analysis, segments research, trends and forecast report 2025 t...

Calcineurin Inhibitor Market growth is projected to reach USD 13.82 Billion, at a 3.32% CAGR by driving industry size, share, top company analysis, segments research, trends and forecast report 2025 t...

Market Overview and Industry Context Calcineurin inhibitors are a critical class of immunosuppressive drugs widely used to prevent organ transplant rejection and manage various autoimmune disorders. Their mechanism involves suppressing T-cell activation, thereby controlling overactive immune responses. As the demand for organ transplantation grows globally and autoimmune diseases become more prevalent, the Calcineurin Inhibitor Market is attracting significant interest from pharmaceutical companies and healthcare stakeholders seeking to capitalize on emerging opportunities.

Introduction

Introduction

Introduction

Calcineurin Inhibitor Market growth is projected to reach USD 13.82 Billion, at a 3.32% CAGR by driving industry size, share, top company analysis, segments research, trends and forecast report 2025 t...

Impaired sperm motility is a leading cause of male infertility. Studies indicated that FK506, an immunosuppressive drug, resulted in male mouse infertility or an overall decline in the fertilization c...

CLMB lacks predicted transmembrane domains but may associate with membranes via lipidation (Fig. 1a)10. CLMB contains a glycine at position 2 (Gly2), a site frequently modified by myristate, a 14-carbon lipid whose co-translational addition can promote protein association with membranes11...

Calcineurin (CaN), a Ca2+-dependent phosphatase, plays key roles in eukaryotic cell signaling. We investigated whether Leishmania amazonensis’ two infective forms—promastigotes and amastigotes—exhibit differences in CaN expression, localization, and functional impact, using two canonical inhibitors (cyclosporin A, CsA; tracolimus, FK506). At high 40 µM CsA, promastigotes showed reduced viability, whereas amastigotes remained resistant. FK506 had no effect on either form. At a sub-lethal 25 µM CsA, parasite proliferation remained unaffected. In parasite–macrophage co-incubation assays, phosphorylation patterns differed: amastigotes—but not promastigotes—showed increased serine/threonine phosphorylation upon CaN inhibition. Western blotting and in silico data revealed higher CaN catalytic (CaNA2) and regulatory (CaNB) subunit expression in amastigotes than promastigotes. Immunofluorescence localized CaNA prominently in both cytoplasm and nucleus of promastigotes, but predominantly cytoplasmic in amastigotes; CaNB was largely cytoplasmic in both. In silico localization predictions suggested strong membrane associations for CaNA in Leishmania, contrasting with mammalian models. Subcellular fractionation confirmed CaNA enrichment in membrane fractions, with CaNB in cytoplasmic and nuclear fractions. Collectively, these findings reveal form-specific differences in expression, subcellular distribution, and inhibitor responses of CaN in L. amazonensis, highlighting its potential as a stage-specific therapeutic target in leishmaniasis.

Calcineurin (CaN), a Ca2+-dependent phosphatase, plays key roles in eukaryotic cell signaling. We investigated whether Leishmania amazonensis’ two infective forms—promastigotes and amastigotes—exhibit differences in CaN expression, localization, and functional impact, using two canonical inhibitors (cyclosporin A, CsA; tracolimus, FK506). At high 40 µM CsA, promastigotes showed reduced viability, whereas amastigotes remained resistant. FK506 had no effect on either form. At a sub-lethal 25 µM CsA, parasite proliferation remained unaffected. In parasite–macrophage co-incubation assays, phosphorylation patterns differed: amastigotes—but not promastigotes—showed increased serine/threonine phosphorylation upon CaN inhibition. Western blotting and in silico data revealed higher CaN catalytic (CaNA2) and regulatory (CaNB) subunit expression in amastigotes than promastigotes. Immunofluorescence localized CaNA prominently in both cytoplasm and nucleus of promastigotes, but predominantly cytoplasmic in amastigotes; CaNB was largely cytoplasmic in both. In silico localization predictions suggested strong membrane associations for CaNA in Leishmania, contrasting with mammalian models. Subcellular fractionation confirmed CaNA enrichment in membrane fractions, with CaNB in cytoplasmic and nuclear fractions. Collectively, these findings reveal form-specific differences in expression, subcellular distribution, and inhibitor responses of CaN in L. amazonensis, highlighting its potential as a stage-specific therapeutic target in leishmaniasis.