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Vildagliptine protects SH-SY5Y human neuron-like cells from A? 1-42 induced toxicity, in vitro.

ABSTRACT: The amyloid ? (A?) toxic fibrils is thought to play a central role in the onset and progression of Alzheimer's disease (AD) because of it is a main formation of senile plaques. Diabetic patients are more vulnerable to caught Alzheimer's disease. Vildagliptine, a novel anti diabetic agent, has been reported to exert protective effects on AD rat models in restricted study. We aimed to investigate any protective effects of vildagliptine against A? fibrils on SH-SY5Y cell line. Vildagliptine decreased PSEN1 and PSEN2 mRNA levels which enroll A? production. In addition, vildagliptin was downregulated caspase-3 and caspase-9 expression levels which were evoked by A?. Also we confirmed cellular viability with real time cell analyzer and MTT assay. Our data exposed that vildagliptine has lowering effect on GSK3? and Tau phosphorylation. However we did not get protective effect of vildagliptine against A? toxicity on mitochondrial membrane potential. These results indicate that vildagliptine exerts a protective effect against A? by decreasing apoptosis related proteins, lowering GSK3? and Tau phosphorylation levels in addition to expression of PSEN1 and PSEN2 mRNA downregulation effect.

SUBMITTER: Dokumac? AH

PROVIDER: S-EPMC6465375 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Vildagliptine protects SH-SY5Y human neuron-like cells from Aβ 1-42 induced toxicity, in vitro.

Dokumacı Alim Hüseyin AH Yerer Aycan Mukerrem Betul MB

Cytotechnology 20190409 2

The amyloid β (Aβ) toxic fibrils is thought to play a central role in the onset and progression of Alzheimer's disease (AD) because of it is a main formation of senile plaques. Diabetic patients are more vulnerable to caught Alzheimer's disease. Vildagliptine, a novel anti diabetic agent, has been reported to exert protective effects on AD rat models in restricted study. We aimed to investigate any protective effects of vildagliptine against Aβ fibrils on SH-SY5Y cell line. Vildagliptine decreas ...[more]

PMID: 30968232

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Project description:Alzheimer's disease (AD) is the most common form of dementia and has no cure. Therapeutic strategies focusing on the reduction of oxidative stress, modulation of amyloid-beta (Aβ) toxicity and inhibition of tau protein hyperphosphorylation are warranted to avoid the development and progression of AD. The aim of this study was to screen the crude extracts (CEs) and ethyl-acetate fractions (EAFs) of Guazuma ulmifolia, Limonium brasiliense, Paullinia cupana, Poincianella pluviosa, Stryphnodendron adstringens and Trichilia catigua using preliminary in vitro bioassays (acetylcholinesterase inhibition, antioxidant activity and total polyphenol content) to select extracts/fractions and assess their protective effects against Aβ25-35 toxicity in SH-SY5Y cells. The effect of the EAF of S. adstringens on mitochondrial membrane potential, lipid peroxidation, superoxide production and mRNA expression of 10 genes related to AD was also evaluated and the electropherogram fingerprints of EAFs were established by capillary electrophoresis. Chemometric tools were used to correlate the in vitro activities of the samples with their potential to be evaluated against AD and to divide extracts/fractions into four clusters. Pretreatment with the EAFs grouped in cluster 1 (S. adstringens, P. pluviosa and L. brasiliense) protected SH-SY5Y cells from Aβ25-35-induced toxicity. The EAF of S. adstringens at 15.62 μg/mL was able completely to inhibit the mitochondrial depolarization (69%), superoxide production (49%) and Aβ25-35-induced lipid peroxidation (35%). With respect to mRNA expression, the EAF of S. adstringens also prevented the MAPT mRNA overexpression (expression ratio of 2.387x) induced by Aβ25-35, which may be related to tau protein hyperphosphorylation. This is the first time that the neuroprotective effects of these fractions have been demonstrated and that the electropherogram fingerprints for the EAFs of G. ulmifolia, L. brasiliense, P. cupana, P. pluviosa and S. adstringens have been established. The study expands knowledge of the in vitro protective effects and quality control of the evaluated fractions.

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Vildagliptine protects SH-SY5Y human neuron-like cells from A? 1-42 induced toxicity, in vitro.

Publications

Vildagliptine protects SH-SY5Y human neuron-like cells from Aβ 1-42 induced toxicity, in vitro.

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