Alterations in Tryptophan Metabolism Affect Vascular Functions: Connected to Ageing Population Vulnerability to COVID-19 Infection?

[摘要] The essential amino acid tryptophan is the unique substratefor the biosynthesis of neurotransmitter serotonin, sleep hormone melatonin and co-factor nicotinamide adenine dinucleotide (NAD+) through its metabolic pathways.1 Thecatabolism of tryptophan by indoleamine 2,3-dioxygenases(IDO1/2) through the kynurenine pathway (KP) leads to thegeneration of multiple bioactive metabolites referred askynurenines.2,3 Within the central nervous system (CNS),brain cells including glia and neurons produce differentkynurenines.4 During ageing a shift from the serotonergic tokynurenine pathway progressively occurs in the tryptophancatabolism resulting in an increased activity of the enzymeIDO-1 in turn increases the production of neuroactive KPmetabolites.5 The progressive alterations of the innateimmune system linked to ageing trigger the development ofchronic inflammatory cascades referred as ‘inflammaging’which include astrogliosis, microgliosis and increased production of cytokines like IL-6, IL-1β, IFN-γ, TNF-αetc. . ..2,6 IFN-γ and TNF-α are both know to trigger astrong induction of IDO1 through positive feedback mechanism in older population.7 This increased IDO1 activity withage not only results in higher production of kynurenines, butalso stimulates inducible nitric oxide synthase (iNOS) activity and increases nitric oxide (NO) production.

[学科分类] 生理学与病理学

[关键词] Covid-19;kynurenines;neurodegeneration;cerebrovascular;cognition