Kynurenine Pathway and Its Metabolites in Autism Spectrum Disorder: a Close Link
- VernacularTitle:犬尿氨酸代谢及其代谢产物与孤独症谱系障碍的内在关联
- Author:
Ya-Qian XIAO
1
;
Li-Chen QIAO
1
;
De-Chang RONG
1
;
Yu-Chen LEI
1
;
Hakan ÜREY
2
;
Lan-Lan ZUO
1
;
Hasan BAYRAM
3
;
Reza A. GHILADI
4
;
Yi-Fan DUAN
1
;
Meng-Jiao LI
1
Author Information
- Publication Type:Journal Article
- Keywords: autism spectrum disorder (ASD); redox imbalance; abnormal ncRNA expression; disruption of the “gut-brain axis”; pathogenic mechanisms of ASD; ASD diagnosis and treatment
- From: Progress in Biochemistry and Biophysics 2026;53(9):2402-2413
- CountryChina
- Language:English
- Abstract: Kynurenine pathway (KP) is a major catabolic route of tryptophan, generating a series of bioactive metabolites including kynurenine, kynurenic acid (KA), quinolinic acid, and 3-hydroxykynurenine. Beyond its fundamental role in amino acid metabolism, KP exerts critical regulatory functions in neurodevelopment, synaptic plasticity, and immune modulation. Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with onset in early childhood, characterized by persistent deficits in social communication and restricted, repetitive behaviors. Despite extensive research, the etiological mechanisms underlying ASD remain highly complex and incompletely understood, involving genetic, environmental, and immunological factors. Emerging clinical evidence has consistently revealed a significant imbalance in KP metabolites in individuals with ASD, often accompanied by altered ratios of neuroprotective versus neurotoxic byproducts. However, the primary drivers of this metabolic dysregulation and its causative contribution to ASD pathogenesis are not yet fully elucidated. In this review, we systematically review the enzymatic steps of KP and the principal physiological functions of its major metabolites, with particular emphasis on their dual roles in neuroprotection and neurotoxicity. We then analyze the potential pathogenic mechanisms through which KP dysfunction may contribute to ASD, focusing on two interconnected etiological dimensions. First, KP imbalance can promote oxidative stress, which in turn triggers chronic inflammatory responses via microglial activation and release of pro-inflammatory cytokines, thereby disrupting neuronal homeostasis. Second, aberrant KP metabolism affects neurotransmitter systems, particularly glutamatergic and dopaminergic signaling, leading to impaired neural circuit development and synaptic pruning. By integrating current findings on the KP-ASD association, this review offers a comprehensive etiological framework and a clinically relevant paradigm. Furthermore, we highlight that specific KP metabolites, such as the KA/quinolinic acid ratio, hold promise as peripheral biomarkers for early diagnosis and disease stratification. Finally, we discuss the therapeutic potential of targeting KP enzymes or receptors for personalized intervention strategies, while acknowledging the challenges in translating these findings into clinical practice.
