Inflammatory cytokine upd3 induces axon length-dependent synapse removal by glia.

ABSTRACT: Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors but the cellular and molecular bases for neurite length-dependent vulnerability of neurons to degeneration is largely unknown. Using Drosophila sensory neurons as a model system we show that neuronal activation of the integrated stress response triggers expression of the Interleukin-6 homolog unpaired 3 (upd3), which is both necessary and sufficient for axon length-dependent degeneration of presynapses. Upd3 activates phagocytic glia, triggering phagocytic removal of presynapses preferentially on neurons with long axons, thus revealing an intrinsic axon length-dependent vulnerability to glial insult. Finally, we found that axon length-dependent presynapse loss in fl

SUBMITTER: Tenedini FM 

PROVIDER: S-EPMC12130839 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature