| Title |
Neuronal sphingosine kinase 2 subcellular localization is altered in Alzheimer’s disease brain
|
|---|---|
| Published in |
Acta Neuropathologica Communications, April 2018
|
| DOI | 10.1186/s40478-018-0527-z |
| Pubmed ID | |
| Authors |
Gaëlle Dominguez, Marie-Lise Maddelein, Mélanie Pucelle, Yvan Nicaise, Claude-Alain Maurage, Charles Duyckaerts, Olivier Cuvillier, Marie-Bernadette Delisle |
| Abstract |
Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) peptides and hyperphosphorylated tau protein accompanied by neuronal loss. Aβ accumulation has been associated with an impaired sphingosine 1-phosphate (S1P) metabolism. S1P is generated by sphingosine kinases (SphKs), of which there are two isoenzymes SphK1 and SphK2, and degraded by the sphingosine 1-phosphate lyase (SPL). We previously reported, that both a decrease in SphK1 expression and an increase in SPL expression, correlated with amyloid deposits in the entorhinal cortex of AD brains, suggesting a global loss of pro-survival S1P in AD neurons. SphK2 contribution has also been examined in AD yielding to conflicting results that may reflect the complexity of SphK2 regulation. The subcellular localization of SphK2, hence the compartmentalization of generated S1P, is recognized to play a crucial role in dictating either its pro-survival or pro-apoptotic functions. We therefore aimed at studying the expression of SphK2 and notably its subcellular localization in brain tissues from patients with AD. We report that a decrease in SphK2 protein cytosolic expression correlated with the density of amyloid deposits in a cohort of 25 post-mortem brains. Interestingly, we observed that the equilibrium between cytoplasmic and nuclear SphK2 is disrupted and showed that SphK2 is preferentially localized in the nucleus in AD brain extracts as compared to control extracts, with a marked increase of cleaved SphK2. Our results suggest that a shift in the subcellular localization of the S1P generating SphK2 may compromise the well established pro-survival cytosolic S1P by favoring the production of nuclear S1P associated with adverse effects in AD pathogenesis. |
Mendeley readers
The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 53 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 17% |
| Student > Bachelor | 7 | 13% |
| Student > Master | 7 | 13% |
| Researcher | 5 | 9% |
| Student > Doctoral Student | 2 | 4% |
| Other | 5 | 9% |
| Unknown | 18 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 19% |
| Neuroscience | 8 | 15% |
| Medicine and Dentistry | 6 | 11% |
| Nursing and Health Professions | 2 | 4% |
| Agricultural and Biological Sciences | 2 | 4% |
| Other | 2 | 4% |
| Unknown | 23 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 06 April 2018.
All research outputs
#4,229,237
of 23,041,514 outputs
Outputs from Acta Neuropathologica Communications
#782
of 1,394 outputs
Outputs of similar age
#83,945
of 329,118 outputs
Outputs of similar age from Acta Neuropathologica Communications
#15
of 28 outputs
Altmetric has tracked 23,041,514 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,394 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 39th percentile – i.e., 39% of its peers scored the same or lower than it.
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We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.