Date of Completion
Honors College Thesis
Department of Biology
College of Arts and Science Honors, Honors College
Alzheimers disease, glia, Draper, Drosophila, Mcr
In mammals, microglia play the role of the resident macrophage in the central nervous system (CNS), whose duty is to engulf dead neurons, cellular debris, aging synapses and excess synaptic connections during development (Stevens et al., 2007). In Drosophila (fruit flies), cortex glia are a glial subset that play an analogous role to microglia. Draper, an engulfment receptor highly expressed within glia, has been identified as a principal player in engulfment (Freeman et al., 2003). However, the upstream activator of Draper in the Drosophila CNS remains ambiguous. This study explores the role of Macroglobulin complement protein (Mcr), a potential upstream activator of Draper, which is necessary for the engulfment of cellular debris and dead neurons (MacDonald et al., 2006, Ray et al., 2017, McLaughlin et al. 2019). Glial morphology and cross-talk with neurons, along with glial engulfment and regulation of Aβ plaques in the context of Alzheimer’s Disease (AD), is woefully understudied. This project aimed to further elucidate the extent of this communication within normal and Aβ42-expressing Drosophila. Given the recent identification of the role of p38 kinases in multiple sclerosis, another glial-based neurodegenerative disease (Krementsov et al., 2014), the role of p38 kinases in AD is explored through elimination of their glial expression in an Aβ42 background. Preliminary findings suggest that Mcr regulates engulfment through the Draper receptor in a cortex glia-specific fashion, and p38a contributes to the pathological phenotype observed in AD.
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Paige, Zoë A., "Identifying the Impact of Glial Engulfment and Aβ42-induced Nervous System Dysfunction" (2021). UVM Honors College Senior Theses. 428.
Available for download on Friday, May 20, 2022