Abstract
Ferroptosis is a form of regulated cell death resulting from iron accumulation and lipid peroxidation. In some particular brain regions, iron dyshomeostasis and peroxidation damage of neurons are closely related to a wide range of neurodegenerative diseases known as “tauopathies”, in which intracellular aggregation of microtubule-associated protein tau is the common neuropathological feature. However, the relationship between ferroptosis and tau aggregation is not well understood. The current study demonstrates that erastin-induced ferroptosis can promote tau hyperphosphorylation and aggregation in mouse neuroblastoma cells (N2a cells). Moreover, ferroptosis inhibitor ferrostatin-1 can alleviate tau aggregation effectively. In-depth mechanism research indicates that activated Glycogen synthase kinase-3β (GSK-3β) is responsible for abnormal hyperphosphorylation and accumulation. More importantly, proteasome inhibition can exacerbate the tau degradation obstacle and accelerate tau aggregation in the process of ferroptosis. Our results indicate that ferroptosis can lead to abnormal aggregation of tau protein and might be a promising therapeutic target of tauopathies.
Ferroptosis Promotes Microtubule-Associated Protein Tau Aggregation via GSK-3β Activition and Proteasome Inhibition
