| Title |
Alpha-synuclein alters differently gene expression of Sirts, PARPs and other stress response proteins: implications for neurodegenerative disorders
|
|---|---|
| Published in |
Molecular Neurobiology, January 2017
|
| DOI | 10.1007/s12035-016-0317-1 |
| Pubmed ID | |
| Authors |
J. Motyl, P. L. Wencel, M. Cieślik, R. P. Strosznajder, J. B. Strosznajder |
| Abstract |
Alpha-synuclein (ASN) is a presynaptic protein that can easily change its conformation under different types of stress. It's assumed that ASN plays an important role in the pathogenesis of Parkinson's and Alzheimer's disease. However, the molecular mechanism of ASN toxicity has not been elucidated. This study focused on the role of extracellular ASN (eASN) in regulation of transcription of sirtuins (Sirts) and DNA-bound poly(ADP-ribose) polymerases (PARPs) - proteins crucial for cells' survival/death. Our results indicate that eASN enhanced the free radicals level, decreased mitochondria membrane potential, cells viability and activated cells' death. Concomitantly eASN activated expression of antioxidative proteins (Sod2, Gpx4, Gadd45b) and DNA-bound Parp2 and Parp3. Moreover, eASN upregulated expression of Sirt3 and Sirt5, but downregulated of Sirt1, which plays an important role in cell metabolism including Aβ precursor protein (APP) processing. eASN downregulated gene expression of APP alpha secretase (Adam10) and metalloproteinases Mmp2, Mmp10 but upregulated Mmp11. Additionally, expression and activity of pro-survival sphingosine kinase 1 (Sphk1), Akt kinase and anti-apoptotic protein Bcl2 were inhibited. Moreover, higher expression of pro-apoptotic protein Bax and enhancement of apoptotic cells' death were observed. Summarizing, eASN significantly modulates transcription of Sirts and enzymes involved in APP/Aβ metabolism and through these mechanisms eASN toxicity may be enhanced. The inhibition of Sphk1 and Akt by eASN may lead to disturbances of survival pathways. These results suggest that eASN through alteration of transcription and by inhibition of pro-survival kinases may play important pathogenic role in neurodegenerative disorders. |
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 % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 54 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 22% |
| Student > Master | 9 | 17% |
| Researcher | 6 | 11% |
| Student > Bachelor | 4 | 7% |
| Professor | 4 | 7% |
| Other | 6 | 11% |
| Unknown | 13 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 13 | 24% |
| Neuroscience | 10 | 19% |
| Agricultural and Biological Sciences | 6 | 11% |
| Medicine and Dentistry | 3 | 6% |
| Chemistry | 2 | 4% |
| Other | 5 | 9% |
| Unknown | 15 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. 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 June 2019.
All research outputs
#2,638,051
of 23,305,591 outputs
Outputs from Molecular Neurobiology
#316
of 3,533 outputs
Outputs of similar age
#54,963
of 423,326 outputs
Outputs of similar age from Molecular Neurobiology
#8
of 78 outputs
Altmetric has tracked 23,305,591 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,533 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done particularly well, scoring higher than 90% 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 423,326 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 86% of its contemporaries.
We're also able to compare this research output to 78 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 91% of its contemporaries.