The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.
The kynurenine pathway and neurodegenerative disease
Open accessAbstract
Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation have been closely linked to the pathogenesis of several neurodegenerative diseases. Tryptophan is an essential amino acid required for protein synthesis, and in higher eukaryotes is also converted into the key neurotransmitters serotonin and tryptamine. However, in mammals >95% of tryptophan is metabolized through the KP, ultimately leading to the production of nicotinamide adenosine dinucleotide (NAD(+)). A number of the pathway metabolites are neuroactive; e.g. can modulate activity of several glutamate receptors and generate/scavenge free radicals. Imbalances in absolute and relative levels of KP metabolites have been strongly associated with neurodegenerative disorders including Huntington's, Alzheimer's, and Parkinson's diseases. The KP has also been implicated in the pathogenesis of other brain disorders (e.g. schizophrenia, bipolar disorder), as well as several cancers and autoimmune disorders such as HIV. Pharmacological and genetic manipulation of the KP has been shown to ameliorate neurodegenerative phenotypes in a number of model organisms, suggesting that it could prove to be a viable target for the treatment of such diseases. Here, we provide an overview of the KP, its role in neurodegeneration and the current strategies for therapeutic targeting of the pathway.
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“As TLR3 is abundantly expressed in the brain187, abnormal activation of NMDA receptor signalling by quinolinic acid might be at least partially responsible for numerous neurological diseases186,188.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [188]
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Cites
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Metadata
- Authors
- Maddison, D. C., & Giorgini, F.
- Affiliations
- University of Leicester (GB)
- Corresponding author
- Giorgini, Flaviano
- Venue
- Seminars in Cell & Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 40
- Pages
- 134-141
- ISSN
- 1084-9521 (ISSN-L)
- OpenAlex
- W1990201789
- Cited by
- 309
- References
- 94
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 29 · 2023: 30 · 2022: 32 · 2021: 47 · 2020: 33 · 2019: 27 · 2018: 19 · 2017: 21 · 2016: 17 · 2015: 6
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Seminars in Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion, other-oa)
- Funders
- the Midlands Integrative Biosciences Training Partnership (MIBTP)
- the Biotechnology and Biological Sciences Research Council (BBSRC)
- the Medical Research Council (MRC)
- the CHDI Foundation
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- kynurenine pathway, tryptophan metabolism, neurodegenerative diseases, NAD biosynthesis, kynurenine metabolites, glutamate receptors, free radicals, Huntington's disease, Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, HIV, therapeutic targeting, neuroactive metabolites
- MeSH terms
- Animals, Humans, Kynurenine, Tryptophan, Neurodegenerative Diseases, Metabolic Networks and Pathways
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