Журнал болезни Альцгеймера и паркинсонизма

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FTO Knockdown Decreases Phosphorylation of Tau in Neuronal Cells; A Potential Model Implicating the Association of FTO with Alzheimer 's Disease

Ryan T Pitman, Jason T Fong, Amanda L Stone, Joseph T Devito and Neelu Puri

Recent genetic studies identify variants within the Fat Mass and Obesity Associated gene (FTO) as important contributors to the development of obesity and suggest a potential link between obesity-associated FTO variants and Alzheimer’s disease (AD). The mechanisms of association regarding FTO and AD are currently unclear; however, obesity is thought to be a well known risk factor for AD. In Alzheimer’s disease hyperphosphorylation of the Tau protein at certain epitopes causes the formation of neurofibrillary tangles due to microtubule collapse. AMP-activated protein kinase (AMPk) is known to phosphorylate Tau, and previous studies have proposed a relationship between FTO knockdown and phosphorylated AMPk (pAMPk). In this study we show that siRNA mediated knockdown of FTO expression in SH-SY5Y neuroblastoma cells decreases Tau phosphorylation. This novel finding suggests the potential for a cellular mechanism that may link FTO function with the development of AD.