Therapeutic potential of targeting kynurenine pathway in neurodegenerative diseases.
Eur J Med Chem
; 251: 115258, 2023 May 05.
Article
em En
| MEDLINE
| ID: mdl-36917881
ABSTRACT
Kynurenine pathway (KP), the primary pathway of L-tryptophan (Trp) metabolism in mammals, contains several neuroactive metabolites such as kynurenic acid (KA) and quinolinic acid (QA). Its imbalance involved in aging and neurodegenerative diseases (NDs) has attracted much interest in therapeutically targeting KP enzymes and KP metabolite-associated receptors, especially kynurenine monooxygenase (KMO). Currently, many agents have been discovered with significant improvement in animal models but only one aryl hydrocarbon receptor (AHR) agonist 30 (laquinimod) has entered clinical trials for treating Huntington's disease (HD). In this review, we describe neuroactive KP metabolites, discuss the dysregulation of KP in aging and NDs and summarize the development of KP regulators in preclinical and clinical studies, offering an outlook of targeting KP for NDs treatment in future.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Huntington
/
Doenças Neurodegenerativas
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2023
Tipo de documento:
Article