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Kynurenine Metabolism and Alzheimer’s Disease: The Potential Targets and Approaches

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Abstract

l-tryptophan, an essential amino acid, regulates protein homeostasis and plays a role in neurotransmitter-mediated physiological events. It also influences age-associated neurological alterations and neurodegenerative changes. The metabolism of tryptophan is carried majorly through the kynurenine route, leading to the production of several pharmacologically active enzymes, substrates, and metabolites. These metabolites and enzymes influence a variety of physiological and pathological outcomes of the majority of systems, including endocrine, haemopoietic, gastrointestinal, immunomodulatory, inflammatory, bioenergetic metabolism, and neuronal functions. An extensive literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on the kynurenine metabolites that influence cellular redox potential, immunoregulatory mechanisms, inflammatory pathways, cell survival channels, and cellular communication in close association with several neurodegenerative changes. The imbalanced state of kynurenine pathways has found a close association to several pathological disorders, including HIV infections, cancer, autoimmune disorders, neurodegenerative and neurological disorders including Parkinson’s disease, epilepsy and has found special attention in Alzheimer's disease (AD). Kynurenine pathway (KP) is intricately linked to AD pathogenesis owing to the influence of kynurenine metabolites on excitotoxic neurotransmission, oxidative stress, uptake of neurotransmitters, and modulation of neuroinflammation, amyloid aggregation, microtubule disruption, and their ability to induce a state of dysbiosis. Pharmacological modulation of KP pathways has shown encouraging results, indicating that it may be a viable and explorable target for the therapy of AD.

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India for providing the necessary facilities to carry out the research work.

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Authors and Affiliations

  1. Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India

    Vivek Kumar Sharma, Thakur Gurjeet Singh, Nirbhay Kumar Prabhakar & Ashi Mannan

  2. Govt. College of Pharmacy, Rohru, Shimla, Himachal Pradesh, 171207, India

    Vivek Kumar Sharma

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  1. Vivek Kumar Sharma
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Conceptualization: conceived and designed the experiments: TGS. Analyzed the data: VKS, TGS. Wrote the manuscript: VKS. Visualization: VKS, AM, NKP. Editing of the manuscript: VKS, TGS. Critically reviewed the article: TGS. Supervision: TGS. All authors read and approved the final manuscript.

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Correspondence to Thakur Gurjeet Singh.

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Sharma, V.K., Singh, T.G., Prabhakar, N.K. et al. Kynurenine Metabolism and Alzheimer’s Disease: The Potential Targets and Approaches. Neurochem Res 47, 1459–1476 (2022). https://doi.org/10.1007/s11064-022-03546-8

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