Bhumika Ramesh | 2026 I.S. Symposium
Name: Bhumika Ramesh
Title: The Role of Tau and the RNA-Binding Protein Nab2 on Cholinergic Degeneration in GAL4-UAS Drosophila melanogaster Models
Major: Neuroscience
Advisor: Seth Kelly
Alzheimer’s disease (AD) affects over 32 million people worldwide and is characterized by the formation of neurofibrillary tangles composed of pathological tau, causing neuronal loss and cognitive decline. Among the earliest neurons lost in AD are cholinergic neurons, which produce acetylcholine (ACh). The enzymes controlling ACh synthesis and breakdown, ChAT and AChE, depend on proper mRNA processing regulated by RNA-binding proteins (RBPs). Pathological tau disrupts mRNA processing in AD, but whether it specifically targets ChAT and AChE transcripts to potentially cause early cholinergic degeneration is not known. Unlike the overexpression of the RBP ZC3H14, which exacerbates tau accumulation, its Drosophila ortholog Nab2 overexpression lowers tau levels, making Nab2 a candidate to rescue tau-driven cholinergic dysfunction. Therefore, we examined whether tau contributes to cholinergic degeneration by disrupting ChAT and AChE expression, and whether Nab2 overexpression could rescue these changes. We used 18-21 day-old female Drosophila overexpressing tau and Nab2 to examine changes in ChAT and AChE mRNA and protein levels, and visualized cholinergic neurons in the mushroom bodies to analyze ChAT expression via GFP intensity. Our work revealed no changes in the mRNA and protein levels of ChAT and AChE despite overexpressing tau and Nab2. In contrast, the overexpression of tau, as well as Nab2, significantly decreased GFP expression in Drosophila mushroom bodies, suggesting a decrease in ChAT expression and cholinergic neurons. These results indicate that Nab2 overexpression alone is insufficient to rescue tau-induced changes in Drosophila mushroom bodies. This study opens avenues to investigate RBP-tau interactions and whether they can be targeted to treat cholinergic and widespread neurodegeneration in AD.
Posted in Symposium 2026 on May 1, 2026.
