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Inhibition of Glutamate cysteine ligase depletes neuronal glutathione, elevates glutamate and increases excitatory neurotransmission Glutamate cysteine ligase (GCL) is the rate limiting step for glutathione synthesis, and utilizes glutamate as a substrate

Its specific regulatory mechanism is shown in Figure 1

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Under nutrient-rich conditions, mTORC1 phosphorylates the carboxy-terminal serine residues on p300, thereby alleviating its self-inhibition, inhibiting autophagy, and promoting lipogenesis [53]

A future need for this AOP is a vigorous and thorough experiment model system to evaluate dose-response relationships, conentration-response relationships and exposure-effect relationships within the framework of this AOP