The article reviews the role of the glutamate-glutamine cycle (GGC) in astrocyte-neuron interactions and its dysfunction in tau-dependent neurodegeneration. Astrocytes, the most abundant glial cells in the brain, play critical roles in maintaining neuronal homeostasis, including neurotransmitter balance, blood-brain barrier integrity, and ion homeostasis. The GGC is essential for the exchange of glutamate and glutamine between astrocytes and neurons, facilitating neurotransmitter recycling and maintaining synaptic function. In tauopathies, such as Alzheimer's disease, the GGC is disrupted, leading to impaired glutamate clearance and altered neurotransmitter homeostasis, which contributes to neuronal dysfunction and death. The GGC involves the uptake of glutamate by astrocytes, its conversion to glutamine by glutamine synthetase (GS), and the subsequent release of glutamine back to neurons, where it is converted back to glutamate by phosphate-activated glutaminase (PAG). This cycle is crucial for maintaining glutamate homeostasis and preventing excitotoxicity. However, in tauopathies, the dysfunction of GGC components, such as glutamate transporters and glutamine transporters, disrupts this cycle, leading to glutamate accumulation and neuronal damage. The article also discusses the role of astrocyte-neuron interactions in tauopathies, highlighting the involvement of astrocytic exosomal pathways in the propagation of toxic tau aggregates. Astrocytes can contribute to the spread of pathological tau through the release of exosomes containing misfolded tau, which can be taken up by neurons, leading to further neurodegeneration. Additionally, astrocytic reactivity in tauopathies is associated with the loss of neuroprotective functions and the gain of neurotoxic properties, exacerbating neuronal damage. The study emphasizes the importance of understanding the GGC and its disruption in tau-dependent neurodegeneration for developing novel therapeutic strategies. The dysfunction of GGC components, such as glutamate and glutamine transporters, is a key factor in the progression of tauopathies, and targeting these pathways may offer potential treatments for neurodegenerative diseases. The article also highlights the role of astrocyte-microglia interactions in neuroinflammation and the complex roles of astrocytes in both alleviating and contributing to pathology in neurodegenerative diseases.The article reviews the role of the glutamate-glutamine cycle (GGC) in astrocyte-neuron interactions and its dysfunction in tau-dependent neurodegeneration. Astrocytes, the most abundant glial cells in the brain, play critical roles in maintaining neuronal homeostasis, including neurotransmitter balance, blood-brain barrier integrity, and ion homeostasis. The GGC is essential for the exchange of glutamate and glutamine between astrocytes and neurons, facilitating neurotransmitter recycling and maintaining synaptic function. In tauopathies, such as Alzheimer's disease, the GGC is disrupted, leading to impaired glutamate clearance and altered neurotransmitter homeostasis, which contributes to neuronal dysfunction and death. The GGC involves the uptake of glutamate by astrocytes, its conversion to glutamine by glutamine synthetase (GS), and the subsequent release of glutamine back to neurons, where it is converted back to glutamate by phosphate-activated glutaminase (PAG). This cycle is crucial for maintaining glutamate homeostasis and preventing excitotoxicity. However, in tauopathies, the dysfunction of GGC components, such as glutamate transporters and glutamine transporters, disrupts this cycle, leading to glutamate accumulation and neuronal damage. The article also discusses the role of astrocyte-neuron interactions in tauopathies, highlighting the involvement of astrocytic exosomal pathways in the propagation of toxic tau aggregates. Astrocytes can contribute to the spread of pathological tau through the release of exosomes containing misfolded tau, which can be taken up by neurons, leading to further neurodegeneration. Additionally, astrocytic reactivity in tauopathies is associated with the loss of neuroprotective functions and the gain of neurotoxic properties, exacerbating neuronal damage. The study emphasizes the importance of understanding the GGC and its disruption in tau-dependent neurodegeneration for developing novel therapeutic strategies. The dysfunction of GGC components, such as glutamate and glutamine transporters, is a key factor in the progression of tauopathies, and targeting these pathways may offer potential treatments for neurodegenerative diseases. The article also highlights the role of astrocyte-microglia interactions in neuroinflammation and the complex roles of astrocytes in both alleviating and contributing to pathology in neurodegenerative diseases.