Evaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin

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dc.authorid0000-0002-7248-7933
dc.contributor.authorKocanci, Fatma Gonca
dc.contributor.authorSarban, Hamiyet Eciroglu
dc.contributor.authorYildiz, Fatma
dc.date.accessioned2026-01-24T12:31:00Z
dc.date.available2026-01-24T12:31:00Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractNeurodegenerative diseases (ND), marked by progressive neuronal degeneration, often involve dysregulation of acetylcholinesterase (AChE), a key enzyme in cholinergic neurotransmission. AChE inhibition is a well-established therapeutic strategy for Alzheimer's disease (AD), the most prevalent ND, as it aims to restore impaired cholinergic function. However, the effects of calcineurin inhibitors (CNIs), primarily used as immunosuppressants, on AChE activity remain largely unexplored. Recent evidence suggests CNIs possess neuroprotective properties, highlighting their potential for ND treatment. This study evaluated the binding affinities of FDA-approved CNIs-Tacrolimus (Tac), Pimecrolimus (Pim), Cyclosporine A (Csa), and Voclosporin (Voc)-to AChE via molecular docking and molecular dynamic simulation. AChE inhibition was assessed in vitro using the Ellman method and in H2O2-induced degenerative neuron-like SH-SY5Y cells via ELISA and qRT-PCR. Neuroprotection was examined through MTT assays and neurite analysis. Additionally, the antiapoptotic effect was examined by ELISA analysis measuring caspase-3. Docking studies confirmed strong AChE binding for all CNIs, with Voc exhibiting the highest affinity. Voc demonstrated superior in vitro AChE inhibition, surpassing galantamine at low concentrations. Cellular assays showed that CNIs, particularly Voc, significantly inhibited AChE expression at the gene level. Moreover, Voc markedly restored cell viability and reduced neuronal degeneration in H2O2-treated cells. These findings suggest CNIs, especially Voc, as promising candidates for ND treatment, targeting AChE overactivity and oxidative stress.Graphical AbstractCreated in BioRender. Hamiyet Eciroglu Sarban, (2025) https://BioRender.com/q77r137
dc.description.sponsorshipScientific and Technological Research Council of Tuerkiye (TUEBIdot;TAK); President of the Turkish Health Institutes (TUSEB) [32126]
dc.description.sponsorshipFunding Open access funding provided by the Scientific and Technological Research Council of Tuerkiye (TUEB & Idot;TAK). This work was financially supported by the President of the Turkish Health Institutes (TUSEB) (No. 32126).
dc.identifier.doi10.1007/s12035-025-05149-0
dc.identifier.endpage16616
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.issue12
dc.identifier.pmid40952625
dc.identifier.scopus2-s2.0-105016193890
dc.identifier.scopusqualityQ1
dc.identifier.startpage16592
dc.identifier.urihttps://doi.org/10.1007/s12035-025-05149-0
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5582
dc.identifier.volume62
dc.identifier.wosWOS:001571186300001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Neurobiology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260121
dc.subjectAcetylcholinesterase (AChE)
dc.subjectCalcineurin inhibitor drugs
dc.subjectNeuroprotection
dc.subjectOxidative stress
dc.subjectMolecular docking
dc.titleEvaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin
dc.typeArticle

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