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| Title |
The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy
|
|---|---|
| Published in |
Bioscience Reports, August 2023
|
| DOI | 10.1042/bsr20230595 |
| Pubmed ID | |
| Authors |
Abdulla Abu-Bakr Badawy |
| Abstract |
SARS-CoV-2 (COVID-19) exerts profound changes in the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism that may underpin its pathophysiology. The KP is the main source of the vital cellular effector NAD+ and intermediate metabolites that modulate immune and neuronal functions. Trp metabolism is the top pathway influenced by COVID-19. Sixteen studies established virus-induced activation of the KP mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO1) in most affected tissues and of IDO2 in lung by the increased release of proinflammatory cytokines, but could additionally involve increased flux of plasma free Trp and induction of Trp 2,3-dioxygenase (TDO) by cortisol. The major Kyn metabolite targeted by COVID-19 is kynurenic acid (KA), the Kyn metabolite with the greatest affinity for the aryl hydrocarbon receptor (AhR), which is also activated by COVID-19. AhR activation initiates two important series of events: a vicious circle involving IDO1 induction, KA accumulation and further AhR activation, and activation of poly (ADP-ribose) polymerase (PARP) leading to NAD+ depletion and cell death. The virus further deprives the host of NAD+ by inhibiting its main biosynthetic pathway from quinolinic acid, while simultaneously acquiring NAD+ by promoting its synthesis from nicotinamide in the salvage pathway. Additionally, the protective effects of sirtuin 1 are minimised by the PARP activation. KP dysfunction may also underpin the mood and neurological disorders acutely and during "long COVID". More studies of potential effects of vaccination therapy on the KP are required and exploration of therapeutic strategies involving modulation of the KP changes are proposed. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 3 | 8% |
| United States | 1 | 3% |
| Unknown | 34 | 89% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 34 | 89% |
| Scientists | 2 | 5% |
| Practitioners (doctors, other healthcare professionals) | 2 | 5% |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 23 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 17% |
| Student > Bachelor | 3 | 13% |
| Unspecified | 2 | 9% |
| Other | 2 | 9% |
| Student > Ph. D. Student | 2 | 9% |
| Other | 6 | 26% |
| Unknown | 4 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 4 | 17% |
| Agricultural and Biological Sciences | 3 | 13% |
| Unspecified | 2 | 9% |
| Nursing and Health Professions | 2 | 9% |
| Chemical Engineering | 1 | 4% |
| Other | 6 | 26% |
| Unknown | 5 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 18. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 July 2024.
All research outputs
#2,169,138
of 26,415,999 outputs
Outputs from Bioscience Reports
#48
of 2,075 outputs
Outputs of similar age
#37,509
of 367,705 outputs
Outputs of similar age from Bioscience Reports
#1
of 23 outputs
Altmetric has tracked 26,415,999 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,075 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one has done particularly well, scoring higher than 97% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 367,705 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.