Implications for the kynurenine pathway and quinolinic acid in amyotrophic lateral sclerosis
Abstract
The kynurenine pathway (KP) is a major route of L-tryptophan catabolism leading to production of several neurobiologically active molecules. Among them is the excitotoxin quinolinic acid (QUIN) that is known to be involved in the pathogenesis of several major inflammatory neurological diseases. In amyotrophic lateral sclerosis (ALS) degeneration of motor neurons is associated with a chronic and local inflammation (presence of activated microglia and astrocytes). There is emerging evidence that the KP is important in ALS. Recently, we demonstrated that QUIN is significantly increased in serum and CSF of ALS patients. Moreover, most of the factors associated with QUIN toxicity are found in ALS, implying that QUIN may play a substantial role in the neuropathogenesis of ALS. This review details the potential role the KP has in ALS and advances a testable hypothetical model.
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Quinolinic acid, a QUIN precursor, contributes to neuroinflammation and is implicated in various neurodegenerative diseases.
“previous studies showing that quinolinic acid (QA), a QUIN precursor, contributes to neuroinflammation and is implicated in various neurodegenerative diseases [55,56,57].”
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Ogunruku, O. O., Oboh, G., & Ademosun, A. (2014) · International journal of food Science · doi:10.1155/2014/605618 · Cited by 12 · see citing works
“Quinolinic acid (QA) had been reported to activate neurons expressing NMDA receptors and glutamate-type excitotoxicity [36].”
BackgroundAmyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach
Kumar, A., Ghosh, D., & Singh, R. (2013) · Journal of Biomarkers · doi:10.1155/2013/538765 · Cited by 12 · see citing works
“With respect to the pathogenesis of ALS, there is increasing evidence suggesting the involvement of the KP [72], especially that of the neurotoxin QUIN.”
BackgroundTryptophan Metabolism Through the Kynurenine Pathway in Glial Cells
Argolo, D. S., de Oliveira, L. M. G., Guillemin, G. J., Barreto, G. E., Butt, A. M., Costa, S. L., & Costa, M. D. F. D. (2025) · Neuroglia · doi:10.3390/neuroglia6010014 · Cited by 10 · see citing works
“A decrease in the elimination of these oligomers significantly contributes to the pathogenesis of AD [26,42].”
InfluentialSelf-citationFluorometric Determination of Quinolinic Acid Using the Catalytic Activity of Horseradish Peroxidase
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Role of Inflammation in Psychiatric Disease
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A(a)LS: Ammonia-induced amyotrophic lateral sclerosis
Parekh, B. K. (2015) · F1000Research · doi:10.12688/f1000research.6364.1 · Cited by 7 · see citing works
“18 Emerging data indicate a role of QUIN in ALS[193].”
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Self-citationSpectral investigation and theoretical study of zwitterionic and neutral forms of quinolinic acid
Karabacak, M., Sinha, L., Prasad, O., Bilgili, S., Sachan, A. K., Asiri, A. M., & Ataç, A. (2015) · doi:10.1016/j.molstruc.2015.04.010 · Cited by 7
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“Repeatedly, elevations in the KYN/tryptophan ratio, QA/PA, and/or QA/KA ratios have been linked to the development of neurological conditions such as Alzheimer’s disease (32-35), Huntington’s disease (36, 37), AIDS/HIV-associated neurocognitive disorder (38-40), Parkinson’s disease (41), amyotrophic lateral sclerosis…”
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Blaylock, R. L. (2025) · Surgical Neurology International · doi:10.25259/sni_1114_2024 · Cited by 5 · see citing works
“[26,47,25,71,76,86] As an autoimmune disease, as well as elevated glutamate, both increase inflammation one would expect elevation of QUIN in all cases of systemic and CNS inflammation.”
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“TRP is also a precursor to the kynurenine pathway, a pro-inflammatory pathway implicated in numerous neurodegenerative diseases, including ALS (Maddison and Giorgini 2015; Guillemin et al. 2005).”
Potential Mechanism of Cellular Uptake of the Excitotoxin Quinolinic Acid in Primary Human Neurons
Braidy, N., Alicajic, H., Pow, D. V., Smith, J. R., Jugder, B., Brew, B. J., Nicolazzo, J. A., & Guillemin, G. J. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02046-6 · Cited by 12 · see citing works
Self-citation
- Authors
- Guillemin, G. J., Meininger, V., & Brew, B. J.
- Affiliations
- UNSW Sydney (AU)
- St Vincent's Hospital Sydney (AU)
- Venue
- Neurodegenerative Diseases
- Publisher
- S. Karger AG
- Published
- 2005
- Volume
- 2
- Issue
- 3-4
- Pages
- 166-176
- ISSN
- 1660-2854 (ISSN-L)
- 1660-2862
- OpenAlex
- W1978388803
- Cited by
- 105
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 10
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurodegenerative Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- kynurenine pathway, quinolinic acid, amyotrophic lateral sclerosis, excitotoxicity, neuroinflammation, microglial activation, astrocytes, motor neuron degeneration, neuropathogenesis
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Humans, Inflammation, Kynurenine, Models, Neurological, Motor Neurons, Superoxide Dismutase, Signal Transduction, Quinolinic Acid
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