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• W2071080374 startingPage "122" @default.
• W2071080374 abstract "In a previous work we have shown that exposure to aluminum (Al) chloride (AlCl3) enhanced the neurotoxicity of the amyloid beta25-35 fragment (Abeta25-35) in neuroblastoma cells and affected the expression of Alzheimer's disease (AD)-related genes. Caffein, a compound endowed with beneficial effects against AD, exerts neuroprotection primarily through its antagonist activity on A2A adenosine receptors (A2AR), although it also inhibits A1Rs with similar potency. Still, studies on the specific involvement of these receptors in neuroprotection in a model of combined neurotoxicity (Abeta25-35 + AlCl3) are missing. To address this issue, cultured SH-SY5Y cells exposed to Abeta25-35 + AlCl3 were assessed for cell viability, morphology, intracellular ROS activity and expression of apoptosis-, stress- and AD-related proteins. To define the role of A1R and A2ARs, pretreatment with caffein, specific receptor antagonists (DPCPX or SCH58261) or siRNA-mediated gene knockdown were delivered. Results indicate that AlCl3 treatment exacerbated Abeta25-35 toxicity, increased ROS production, lipid peroxidation, β-secretase-1 (BACE1) and amyloid precursor protein (APP). Interestingly, SCH58261 successfully prevented toxicity associated to Abeta25-35 only, whereas pretreatment with both DPCPX and SCH58261 was required to fully avert Abeta25-35 + AlCl3-induced damage, suggesting that A1Rs might also be critically involved in protection during combined toxicity. The effects of caffein were mimicked by both N-acetyl cysteine, an antioxidant, and desferrioxamine, likely acting through distinct mechanisms. Altogether, our data establish a novel protective function associated with A1R inhibition in the setting of combined Abeta25-35 + AlCl3 neurotoxicity, and expand our current knowledge on the potential beneficial role of caffein to prevent AD progression in subjects environmentally exposed to aluminum." @default.
• W2071080374 created "2016-06-24" @default.
• W2071080374 creator A5013077987 @default.
• W2071080374 creator A5051623099 @default.
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• W2071080374 date "2014-09-01" @default.
• W2071080374 modified "2023-09-27" @default.
• W2071080374 title "Dual blockade of the A1 and A2A adenosine receptor prevents amyloid beta toxicity in neuroblastoma cells exposed to aluminum chloride" @default.
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• W2071080374 doi "https://doi.org/10.1016/j.biocel.2014.07.009" @default.
• W2071080374 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25058312" @default.
• W2071080374 hasPublicationYear "2014" @default.
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