| Title |
Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics
|
|---|---|
| Published in |
Glycoconjugate Journal, July 2016
|
| DOI | 10.1007/s10719-016-9705-z |
| Pubmed ID | |
| Authors |
Naila Rabbani, Mingzhan Xue, Paul J. Thornalley |
| Abstract |
The reactive dicarbonyl metabolite methylglyoxal (MG) is the precursor of the major quantitative advanced glycation endproducts (AGEs) in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. The glyoxalase system in the cytoplasm of cells provides the primary defence against dicarbonyl glycation by catalysing the metabolism of MG and related reactive dicarbonyls. Dicarbonyl stress is the abnormal accumulation of dicarbonyl metabolites leading to increased protein and DNA modification contributing to cell and tissue dysfunction in ageing and disease. It is produced endogenously by increased formation and/or decreased metabolism of dicarbonyl metabolites. Dicarbonyl stress contributes to ageing, disease and activity of cytotoxic chemotherapeutic agents. It contributes to ageing through age-related decline in glyoxalase 1 (Glo-1) activity. Glo-1 has a dual role in cancer as a tumour suppressor protein prior to tumour development and mediator of multi-drug resistance in cancer treatment, implicating dicarbonyl glycation of DNA in carcinogenesis and dicarbonyl-driven cytotoxicity in mechanism of action of anticancer drugs. Glo-1 is a driver of cardiovascular disease, likely through dicarbonyl stress-driven dyslipidemia and vascular cell dysfunction. Dicarbonyl stress is also a contributing mediator of obesity and vascular complications of diabetes. There are also emerging roles in neurological disorders. Glo-1 responds to dicarbonyl stress to enhance cytoprotection at the transcriptional level through stress-responsive increase of Glo-1 expression. Small molecule Glo-1 inducers are in clinical development for improved metabolic, vascular and renal health and Glo-1 inhibitors in preclinical development for multidrug resistant cancer chemotherapy. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 50% |
| United Kingdom | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 85 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Mexico | 1 | 1% |
| Unknown | 84 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 17 | 20% |
| Student > Master | 14 | 16% |
| Student > Bachelor | 12 | 14% |
| Researcher | 8 | 9% |
| Student > Doctoral Student | 6 | 7% |
| Other | 10 | 12% |
| Unknown | 18 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 15 | 18% |
| Medicine and Dentistry | 12 | 14% |
| Chemistry | 10 | 12% |
| Agricultural and Biological Sciences | 10 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 9% |
| Other | 11 | 13% |
| Unknown | 19 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 23 July 2016.
All research outputs
#16,047,334
of 25,373,627 outputs
Outputs from Glycoconjugate Journal
#662
of 929 outputs
Outputs of similar age
#219,667
of 370,095 outputs
Outputs of similar age from Glycoconjugate Journal
#16
of 36 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 929 research outputs from this source. They receive a mean Attention Score of 3.8. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
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 370,095 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.