TOR-Mediated Cell-Cycle Activation Causes Neurodegeneration in a Drosophila Tauopathy Model

摘要: Summary Background Previous studies have demonstrated reexpression of cell-cycle markers within postmitotic neurons in neurodegenerative tauopathies, including Alzheimer's disease (AD). However, the critical questions whether activation is causal or epiphenomenal to tau-induced neurodegeneration and which signaling pathways mediate tauopathy remain unresolved. Results Cell-cycle accompanies wild-type mutant Drosophila , genetically interfering with progression substantially reduces neurodegeneration. Our data support a role for downstream tau phosphorylation, directly preceding apoptosis. We accordingly show that ectopic leads apoptosis vivo. As AD, TOR (target rapamycin kinase) activity increased our model required enhances cell cycle-dependent manner and, when ectopically activated, drives neurons. Conclusions TOR-mediated causes model, identifying cycle as potential therapeutic targets tauopathies AD.