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Mendeley readers
Attention Score in Context
| Title |
Fasudil attenuates aggregation of α-synuclein in models of Parkinson’s disease
|
|---|---|
| Published in |
Acta Neuropathologica Communications, April 2016
|
| DOI | 10.1186/s40478-016-0310-y |
| Pubmed ID | |
| Authors |
Lars Tatenhorst, Katrin Eckermann, Vivian Dambeck, Luis Fonseca-Ornelas, Hagen Walle, Tomás Lopes da Fonseca, Jan C. Koch, Stefan Becker, Lars Tönges, Mathias Bähr, Tiago F. Outeiro, Markus Zweckstetter, Paul Lingor |
| Abstract |
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, yet disease-modifying treatments do not currently exist. Rho-associated protein kinase (ROCK) was recently described as a novel neuroprotective target in PD. Since alpha-synuclein (α-Syn) aggregation is a major hallmark in the pathogenesis of PD, we aimed to evaluate the anti-aggregative potential of pharmacological ROCK inhibition using the isoquinoline derivative Fasudil, a small molecule inhibitor already approved for clinical use in humans. Fasudil treatment significantly reduced α-Syn aggregation in vitro in a H4 cell culture model as well as in a cell-free assay. Nuclear magnetic resonance spectroscopy analysis revealed a direct binding of Fasudil to tyrosine residues Y133 and Y136 in the C-terminal region of α-Syn. Importantly, this binding was shown to be biologically relevant using site-directed mutagenesis of these residues in the cell culture model. Furthermore, we evaluated the impact of long-term Fasudil treatment on α-Syn pathology in vivo in a transgenic mouse model overexpressing human α-Syn bearing the A53T mutation (α-Syn(A53T) mice). Fasudil treatment improved motor and cognitive functions in α-Syn(A53T) mice as determined by Catwalk(TM) gait analysis and novel object recognition (NOR), without apparent side effects. Finally, immunohistochemical analysis revealed a significant reduction of α-Syn pathology in the midbrain of α-Syn(A53T) mice after Fasudil treatment. Our results demonstrate that Fasudil, next to its effects mediated by ROCK-inhibition, directly interacts with α-Syn and attenuates α-Syn pathology. This underscores the translational potential of Fasudil as a disease-modifying drug for the treatment of PD and other synucleinopathies. |
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 Kingdom | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 125 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 125 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 19 | 15% |
| Researcher | 14 | 11% |
| Student > Bachelor | 14 | 11% |
| Student > Doctoral Student | 11 | 9% |
| Student > Master | 11 | 9% |
| Other | 26 | 21% |
| Unknown | 30 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 22 | 18% |
| Biochemistry, Genetics and Molecular Biology | 15 | 12% |
| Agricultural and Biological Sciences | 13 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 6% |
| Medicine and Dentistry | 7 | 6% |
| Other | 24 | 19% |
| Unknown | 37 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 17 January 2022.
All research outputs
#6,310,952
of 22,896,955 outputs
Outputs from Acta Neuropathologica Communications
#908
of 1,386 outputs
Outputs of similar age
#89,437
of 299,032 outputs
Outputs of similar age from Acta Neuropathologica Communications
#19
of 31 outputs
Altmetric has tracked 22,896,955 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,386 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 34th percentile – i.e., 34% 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 299,032 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.