期刊
AGING AND DISEASE
卷 14, 期 3, 页码 858-878出版社
INT SOC AGING & DISEASE
DOI: 10.14336/AD.2022.0916
关键词
central nervous system disease; depression; kynurenine pathway; methoxyindole pathway; neuroinflammation; tryptophan
In this review, the biological properties and pathogenic functions of key metabolites in 12 central nervous system disorders are summarized. The changes in the metabolic pathway of tryptophan and potential therapeutic strategies targeting this pathway are discussed. This comprehensive review provides valuable guidance for future research on neuropsychiatric disorders.
The metabolism of L-tryptophan (TRP) regulates homeostasis, immunity, and neuronal function. Altered TRP metabolism has been implicated in the pathophysiology of various diseases of the central nervous system. TRP is metabolized through two main pathways, the kynurenine pathway and the methoxyindole pathway. First, TRP is metabolized to kynurenine, then kynurenic acid, quinolinic acid, anthranilic acid, 3hydroxykynurenine, and finally 3-hydroxyanthranilic acid along the kynurenine pathway. Second, TRP is metabolized to serotonin and melatonin along the methoxyindole pathway. In this review, we summarize the biological properties of key metabolites and their pathogenic functions in 12 disorders of the central nervous system: schizophrenia, bipolar disorder, major depressive disorder, spinal cord injury, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Furthermore, we summarize preclinical and clinical studies, mainly since 2015, that investigated the metabolic pathway of TRP, focusing on changes in biomarkers of these neurologic disorders, their pathogenic implications, and potential therapeutic strategies targeting this metabolic pathway. This critical, comprehensive, and up-to-date review helps identify promising directions for future preclinical, clinical, and translational research on neuropsychiatric disorders.
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