Surface glia predominantly contribute to the development of ALS/FTD in Drosophila model

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by motor neuron degeneration in the primary motor neurons. C9orf72 repeat expansion mutation is the most prevalent genetic causes of ALS/FTD. Due to the complexity of ALS, there has been no successful therapy for the condition. The traditional neurocentric concept of ALS derives in part from the assumption that the degradation of motor neuron (MN) cells in ALS is driven by cell-autonomous mechanisms, however, recent research has focused on the non-cell-autonomous pathogenic mechanisms such as glial, immune cells and blood-brain barriers participate in the degeneration of MNs in ALS. Drosophila melanogaster is widely used as a genetic model for ALS, giving essential mechanistic data on disease onset and development. Using newly developed genetic tools to individually mark each subtype of the adult glial system in the fruit fly, we demonstrate that surface glia are the major glial subtypes for the pathogenesis of C9orf72-mediated ALS/FTD.

Glia‐specific expression of neuropeptide receptor Lgr4 regulates development and adult physiology in Drosophila

“…We evaluated the lethality of various RNAi strains expressed by tissuespecific GAL4s using two separate methods (Snow et al, 2022). First,…”