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Effect of Three PDEIs on Neuroprotective and Autophagy Proteins in vitro AD Model

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dc.contributor.authorSaygisever-Faikoglu, Kubra
dc.contributor.authorFaikoglu, Gokhan
dc.contributor.authorCelik, Hande
dc.contributor.authorUgur, Sedat Askin
dc.contributor.authorAKKAN, Ahmet Gökhan
dc.contributor.authorKelicen-Ugur, Pelin
dc.contributor.authorOzyazgan, Sibel
dc.contributor.institutionauthorAKKAN, AHMET GÖKHAN
dc.date.accessioned2021-10-19T20:59:16Z
dc.date.available2021-10-19T20:59:16Z
dc.date.issued2021-01-01T00:00:00Z
dc.description.abstractBackground and Objective: The effects of PDEIs on neuroprotective SIRT1 and SESN2, on the autophagy-related proteins, are unknown but neuroprotective enzymes (sirtuins and sestrins) with autophagy genes are involved in the pathogenesis of Alzheimer-s disease. In this study, we aimed to elucidate the effect of three PDE Inhibitors (PDEIs) as autophagy enhancers and provide insights into their neuroprotective effects. Materials and Methods: HT-22 cells were exposed to A$ 25-35 with or without PDEIs for 32 hrs. qRT-PCR was performed for SIRT1, SESN2, ATG5 and BECN1 genes. Western blot analysis was performed for neuroprotective SIRT1, SESN2 proteins and autophagy proteins such as p-mTOR/mTOR, p-AMPK/AMPK and LC3. Results: A$ 25-35 exposure decreased SIRT1, ATG5 and BECN1 expression, while PDEIs prevented these genes from the A$ 25-35 induced decrease. Increased SESN2 gene expression by A$ 25-35 exposure was decreased by PDEIs treatment. Western blot experiment has also shown that SIRT1, p-AMPK and autophagy marker LC3II were decreased, whereas SESN2 and p-mTOR were elevated in the A$ 25-35 exposed HT-22 cells. Co administration of three PDEIs with A$ 25-35 recovered SIRT1, p-AMPK and LC3II decline and compensated SESN2 increase by elevating SIRT1, p-AMPK and LC3II expression and decreasing p-mTOR expression. Conclusion: The present study revealed the significant neuroprotective and autophagy stimulating potential of three PDEIs in A$-induced in vitro AD model. SIRT1 is a novel candidate for determining new, safe and effective treatment strategies and PDEI-mediated SIRT1 increase may advocate autophagy activation through different autophagy components.
dc.identifier.citationSaygisever-Faikoglu K., Faikoglu G., Celik H., Ugur S. A. , AKKAN A. G. , Kelicen-Ugur P., Ozyazgan S., -Effect of Three PDEIs on Neuroprotective and Autophagy Proteins in vitro AD Model-, INTERNATIONAL JOURNAL OF PHARMACOLOGY, cilt.17, sa.4, ss.169-179, 2021
dc.identifier.doi10.3923/ijp.2021.169.179
dc.identifier.urihttp://hdl.handle.net/20.500.12645/29577
dc.identifier.wosWOS:000704553400002
dc.titleEffect of Three PDEIs on Neuroprotective and Autophagy Proteins in vitro AD Model
dc.typeArticle
dspace.entity.typePublication
local.avesis.id50d0b862-fce3-4501-aced-4be986b2ebe4
local.publication.isinternational1
relation.isAuthorOfPublication3d01b102-caf1-4fba-a467-f358f2f6d3c7
relation.isAuthorOfPublication.latestForDiscovery3d01b102-caf1-4fba-a467-f358f2f6d3c7
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