[P2–107]: Combination Therapy of Type 2 Diabetes Medications as a Treatment Target for Alzheimer Disease

Atrakchi‐Baranes, Dana; Lubitz, Irit; Shemesh, Chen; Katsel, Pavel; Liraz‐Zaltsman, Sigal; Licht, Tali; Sharvit‐Ginon, Inbal; Goldman, Shirin Elhaik; Cooper, Itzik; Haroutunian, Vahram; Beeri, Michal Schnaider

doi:10.1016/j.jalz.2017.06.757

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“…Some characteristic features of AD are Amyloid beta (Ab) accumulation, increment of the phosphorilated Tau/Tau level, neurofibrillary tangles, senile plaques and increased activation of prodeath genes and related signaling pathways such as capsapes family (Krajewski et al 1999;Spires-Jones and Hyman 2014). Also up regulation of APP, PSEN1 and PSEN2 expressions, impaired energy metabolism, mitochondrial dysfunction, chronic oxidative stress and DNA damage plays an important role on AD (Atrakchi-Baranes et al 2017;Rivera et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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

Dokumacı

Aycan

2019

Cytotechnology

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The amyloid b (Ab) 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 Ab fibrils on SH-SY5Y cell line. Vildagliptine decreased PSEN1 and PSEN2 mRNA levels which enroll Ab production. In addition, vildagliptin was downregulated caspase-3 and caspase-9 expression levels which were evoked by Ab. Also we confirmed cellular viability with real time cell analyzer and MTT assay. Our data exposed that vildagliptine has lowering effect on GSK3b and Tau phosphorylation. However we did not get protective effect of vildagliptine against Ab toxicity on mitochondrial membrane potential. These results indicate that vildagliptine exerts a protective effect against Ab by decreasing apoptosis related proteins, lowering GSK3b and Tau phosphorylation levels in addition to expression of PSEN1 and PSEN2 mRNA downregulation effect.

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