Publication: Effect of Three PDEIs on Neuroprotective and Autophagy Proteins in vitro AD Model
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2021-01-01T00:00:00Z
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Saygisever-Faikoglu, Kubra
Faikoglu, Gokhan
Celik, Hande
Ugur, Sedat Askin
AKKAN, Ahmet Gökhan
Kelicen-Ugur, Pelin
Ozyazgan, Sibel
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Abstract
Background 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.
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Saygisever-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