Study of the role of Sirtuin1 dSir2 gene in Alzheimer s disease model of Drosophila melanogaster

Abstract

Sirtuins are referred as a Nicotinamide Adenine Dinucleotide (NAD+) dependent class newlineand#1030;and#921;and#921; histone deacetylases enzymes (HDACs). Its plays a key role to control vital cellular functions, such as aging and metabolism. Several studies have shown that it has a protective role against cancer, diabetes, cardiovascular diseases and other agerelated newlineneurodegenerative diseases (NDDs), etc. Sirt1 is a well-studied gene in context to the process of aging and aging is a major risk factor for AD. Thus, in the present study, we have explored the possible genetic interaction between Sirt1 and AD-related genes such as Aand#946;42, Tau and Appl in Drosophila melanogaster. In our study, we have demonstrated that ectopic expression of Aand#946;42, Tau and Appl induced AD-related pathologies such as rough eye phenotype, behavior impairments(Climbing and phototaxis), reduced lifespan, and reduced body weight in Drosophila.We also observed that in AD model flies there is an increased expression of JNK and Notch signaling. Further, the AD-related pathologies were significantly decreased by overexpression of Sirt1and increased when Sirt1was downregulated in AD model flies genetic background. It was demonstrated that AD-related pathologies were associated with reduced expression of the pro-apoptotic gene (Grim, Reaper, and Hid) and increased expression of Drosophila inhibitor of apoptosis protein 1 (diap1) in Sirt1 newlineoverexpression genetic background which ultimately decreased cell death in AD newlinemodel flies. We also observed that JNK and Notch expression was decreased by Sirt1 newlineoverexpression in AD model flies. Thus, based on our observations, we concluded that Sirt1 genetically interacts with AD-related genes (Aand#946;42, Tau and Appl) in Drosophila and has the potential to be used as a therapeutic target for designing the strategies for NDDs. newline