Tumor Necrosis Factor-α Induces Neurotoxicity via Glutamate Release from Hemichannels of Activated Microglia in an Autocrine Manner

Glutamate released by activated microglia induces excitoneurotoxicity and may contribute to neuronal damage in neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis. In addition, tumor necrosis factor-α (TNF-α) secreted from activated microglia may elicit neurodegeneration through caspase-dependent cascades and silencing cell survival signals. However, direct neurotoxicity of TNF-α is relatively weak, because TNF-α also increases production of neuroprotective factors. Accordingly, it is still controversial how TNF-α exerts neurotoxicity in neurodegenerative diseases. Here we have shown that TNF-α is the key cytokine that stimulates…