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Glutamate is the most abundant excitatory neurotransmitter in the central nervous system and a key non-essential amino acid in the body. It plays a central role in maintaining the excitatory-inhibitory balance of the nervous system, regulating systemic metabolic homeostasis, and participating in immune modulation. Additionally, it serves as a precursor for glutathione synthesis. Glutathione is a vital antioxidant and detoxifying molecule in organisms, capable of directly scavenging reactive oxygen species or toxic metabolites. Dysfunction of glutathione is associated with oxidative stress-related diseases. Given the critical roles of glutamate and glutathione in physiological and pathological states, we aim to systematically elucidates the metabolic interplay between glutamate and glutathione, referred to here as the Glutamate-Glutathione axis, as an integrative conceptual framework grounded in established biochemistry. By detailing the metabolic interplay of glutamate and glutathione, this review explores their mutually influential mechanisms. Furthermore, it summarizes the relevant signaling pathways and regulatory mechanisms within the Glutamate-Glutathione axis, clarifying its pivotal role in disease pathogenesis, with a particular focus on neuropsychiatric disorders and cancer. Finally, we aim to review non-invasive methods for detecting glutamate and glutathione using magnetic resonance imaging and presents our specialized sequence. This approach aims to provide a valuable non-invasive imaging tool for early diagnosis, efficacy evaluation, and therapeutic target development in related diseases. By integrating foundational metabolic networks, molecular regulatory mechanisms, disease associations, and clinical detection techniques, this review aim to establish the research framework of the Glutamate-Glutathione axis, fostering deeper integration and advancement from bench to bedside in this field.
Wang et al. (2026) studied this question.