Topic: Brain proteins, microglia and lab models
NAD(P)H quinone oxidoreductase 1 (NQO1) is a multi-functional protein that catalyses the reduction of quinones (and other molecules), thus playing roles in xenobiotic detoxification and redox balance, and also has roles in stabilising apoptosis regulators such as p53. The structure and enzymology of NQO1 is well-characterised, showing a substituted enzyme mechanism in which NAD(P)H binds first and reduces an FAD cofactor in the active site, assisted by a charge relay system involving Tyr-155 and His-161. Protein dynamics play important role in physio-pathological aspects of this protein. NQO1 is a good target to treat cancer due to its overexpression in cancer cells. A polymorphic form of NQO1 (p.P187S) is associated with increased cancer risk and certain neurological disorders (such as multiple sclerosis and Alzheimer´s disease), possibly due to its roles in the antioxidant defence. p.P187S has greatly reduced FAD affinity and stability, due to destabilization of the flavin binding site and the C-terminal domain, which leading to reduced activity and enhanced degradation. Suppressor mutations partially restore the activity of p.P187S by local stabilization of these regions, and showing long-range allosteric communication within the protein. Consequently, the correction of NQO1 misfolding by pharmacological chaperones is a viable strategy, which may be useful to treat cancer and some neurological conditions, targeting structural spots linked to specific disease-mechanisms. Thus, NQO1 emerges as a good model to investigate loss of function mechanisms in genetic diseases as well as to improve strategies to discriminate between neutral and pathogenic variants in genome-wide sequencing studies.
Key findings
- A polymorphic form of NQO1 (p.P187S) is associated with increased cancer risk and certain neurological disorders (such as multiple sclerosis and Alzheimer´s disease), possibly due to its roles in the antioxidant defence. p.P187S has greatly reduced FAD affinity and stability, due to destabilization of the flavin binding site and the C-terminal domain, which leading to reduced activity and enhanced degradation.
Why it matters
This review describes a common form of the NQO1 protein that is associated with increased cancer risk and certain neurological disorders including Alzheimer's disease, possibly through its role in antioxidant defence. It suggests that correcting NQO1 misfolding with pharmacological chaperones is a possible strategy, but this has not been tested as an Alzheimer's treatment.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochimica et biophysica acta. Proteins and proteomics) |
| Journal's citation record | 2 / 4 | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics: journal h-index 160 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 96 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.7 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 5 / 6 | Cited 22.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author David J. Timson: h-index 44 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Universidad de Granada: institution h-index 602 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31091472) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
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Read the original
- DOI: 10.1016/j.bbapap.2019.05.002
- PubMed: 31091472
- Original source →
- Free full text: cris.brighton.ac.uk →
Full text: free to read — Unpaywall lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Beaver, S. K., Mesa-Torres, N., Pey, A. L., & Timson, D. J. (2019). NQO1: A target for the treatment of cancer and neurological diseases, and a model to understand loss of function disease mechanisms. Biochimica et biophysica acta. Proteins and proteomics. https://doi.org/10.1016/j.bbapap.2019.05.002
Vancouver
Beaver SK, Mesa-Torres N, Pey AL, Timson DJ. NQO1: A target for the treatment of cancer and neurological diseases, and a model to understand loss of function disease mechanisms. Biochimica et biophysica acta. Proteins and proteomics. 2019. doi:10.1016/j.bbapap.2019.05.002. PMID: 31091472.
BibTeX
@article{beaver2019-31091472,
author = {Beaver, S. K. and Mesa-Torres, N. and Pey, A. L. and Timson, D. J.},
title = {{NQO1: A target for the treatment of cancer and neurological diseases, and a model to understand loss of function disease mechanisms}},
journal = {Biochimica et biophysica acta. Proteins and proteomics},
year = {2019},
doi = {10.1016/j.bbapap.2019.05.002},
pmid = {31091472},
url = {https://doi.org/10.1016/j.bbapap.2019.05.002}
}
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