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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

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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

Its specific regulatory mechanism is shown in Figure 1

Evidencia (sorafenib): En un estudio de aleatorizado de fase III, con enmascaramiento doble y controlado con placebo (DECISION [NCT00984282]), se evalu el sorafenib en pacientes de cncer de tiroides diferenciado y progresivo resistente a la terapia con yodo.[21] En este ensayo se incluyeron 417 pacientes con cncer de tiroides localmente avanzado o metastsico resistente a la terapia con YRA en los que la enfermedad haba progresado durante los 14 meses previos