Peroxiredoxin 6 Regulates Glia Toxicity in Tau Mediated Neurodegeneration

In Alzheimer’s disease (AD) neurons, which accumulate hyperphosphorylated tau (p‐tau) are associated with neurodegenerative phenotype microglia (MGnD) and A1 neurotoxic astrocytes. MGnD display reduced ability to phagocytose p‐tau aggregates and neuronal remnants, while their pro‐inflammatory character furthers p‐tau accumulation and neuronal demise. Likewise, A1 astrocytes lose their neuron‐supporting function and promote neurodegeneration. Importantly, MGnD and A1 astrocytes reciprocally stimulate their pathological phenotypes. Factors protecting astrocytes form A1 phenotype transformation are unknown. In this work we explored the role of peroxiredoxin (PRDX) 6 in tau mediated neurodegeneration. PRDX6 is an enzymatic protein which in the CNS is unique to astrocytes. It possesses independent glutathione peroxidase and phospholipase 2 enzymatic activities, which confer ability to repair oxidatively damaged cell membranes and cell‐to‐cell signaling.