The article reviews the astrocyte-neuron interaction via the glutamate-glutamine cycle (GGC) and its dysfunction in tau-dependent neurodegeneration. Astrocytes, the largest glial cell type in the brain, play crucial roles in maintaining brain homeostasis, including neurotransmitter regulation, blood-brain barrier maintenance, and neuroprotection. The GGC is a vital pathway for the exchange of glutamate and glutamine between neurons and astrocytes, which is essential for maintaining neurotransmitter homeostasis and energy metabolism. Tauopathies, characterized by the accumulation of hyperphosphorylated tau proteins, are a group of neurodegenerative diseases. The dysfunction of the GGC in tauopathies is highlighted, particularly the disruption of glutamate and glutamine transporters, which leads to impaired astrocyte-neuron communication and neuronal dysfunction. The study also discusses the role of astrocytes in neurodegeneration, including reactive astrogliosis and the release of toxic factors through exosomes. Experimental evidence shows that mutant tau proteins reduce neuronal survival by affecting astrocyte-neuron interactions and disrupting the GGC. The article concludes that understanding the GGC's role in tau-dependent neurodegeneration is crucial for developing novel therapeutic strategies.The article reviews the astrocyte-neuron interaction via the glutamate-glutamine cycle (GGC) and its dysfunction in tau-dependent neurodegeneration. Astrocytes, the largest glial cell type in the brain, play crucial roles in maintaining brain homeostasis, including neurotransmitter regulation, blood-brain barrier maintenance, and neuroprotection. The GGC is a vital pathway for the exchange of glutamate and glutamine between neurons and astrocytes, which is essential for maintaining neurotransmitter homeostasis and energy metabolism. Tauopathies, characterized by the accumulation of hyperphosphorylated tau proteins, are a group of neurodegenerative diseases. The dysfunction of the GGC in tauopathies is highlighted, particularly the disruption of glutamate and glutamine transporters, which leads to impaired astrocyte-neuron communication and neuronal dysfunction. The study also discusses the role of astrocytes in neurodegeneration, including reactive astrogliosis and the release of toxic factors through exosomes. Experimental evidence shows that mutant tau proteins reduce neuronal survival by affecting astrocyte-neuron interactions and disrupting the GGC. The article concludes that understanding the GGC's role in tau-dependent neurodegeneration is crucial for developing novel therapeutic strategies.