The significance of dysregulated serine metabolism in depression

Serine is a non-essential amino acid that supports multiple key metabolic processes, including the synthesis of proteins, amino acids, and glutathione. The central or peripheral dysregulation of serine metabolism in patients with depression has sparked interest in targeted treatment of serine metabolism, particularly D-amino acid oxidase (DAAO) and neuroactive metabolites such as phosphatidylserine (PS), creatine, and sarcosine. This article elaborates on the synthesis and metabolic pathways of serine, including a series of metabolites involved in pathological processes such as excitotoxicity and neuroinflammation, which are closely related to depression. In addition, we elucidate the downstream regulatory role of serine metabolism, including glutamate receptors (glycine receptor, N-methyl-D-aspartate receptor (NMDAR), and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR)), brain-derived neurotrophic factor (BDNF)- tropomyosin-related kinase receptor B (TrkB) signaling pathway, and immune regulation. In summary, serine metabolism dysregulation is closely related to the etiology and pathogenesis of depression, and regulating serine metabolism may be the key to intervening in neuroinflammation, providing a new therapeutic target for depression.