Knocking down key Autophagy and Lysosome Genes in Drosophila Melanogaster to Demonstrate Their Potential Pathological Role in Alzheimer’s disease

Event Center BC

Alzheimer’s disease (AD) is a neurodegenerative disorder that despite extensive efforts, scientists have failed to unlock its pathological mechanism. The hallmark of Alzheimer’s disease is the widespread of two misfolded proteins; Amyloid beta 1-42 and Tau. The AD causes a gradual memory and motor decline and eventual death in human. Currently 5 million Americans and 35 million people worldwide are affected with AD, and those figures are predicted to double by 2050, so there a desperate need for an effective mechanism based treatment. In this study, different autophagy and lysosome genes were knocked down in amyloid beta 1-42 Drosophila model to investigate their potential role in AD. These genes are Atg16¬¬¬A ¬, Atg16B, Atg5, Atg12, and Rab5. We have utilized the binary genetic system, Gal4-UAS to drive the expression of Amyloid beta 1-24 (Aß1-42¬) and knockdown these genes in cholinergic neurons. Genetic crosses were made to create the appropriate strains. Moreover, behavioral tests were performed to assess the resulted strains, both mental and motor functions under controlled and standardized conditions. Also, a robust flow cytometric analysis was performed on the strains’ neuronal cells. Initial results have indicated that rab5 gene was lethal for females in F1 generation. Also, both Atg5 and Atg12 strains have poorly performed on climbing and survival assays compared to Atg16¬¬¬A ¬and Atg16B. Cytometric analysis have indicated an increased internal complexity in neurons derived from these strains which can be attributed to Aß1-42 aggregates and its potential role in causing a dysfunctional enlarged autophagy vesicles inside neurons.