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X Demographics
Mendeley readers
Attention Score in Context
| Title |
A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy
|
|---|---|
| Published in |
Frontiers in Molecular Neuroscience, January 2018
|
| DOI | 10.3389/fnmol.2017.00447 |
| Pubmed ID | |
| Authors |
Karima Schwab, Silke Frahm, David Horsley, Janet E. Rickard, Valeria Melis, Elizabeth A. Goatman, Mandy Magbagbeolu, Morag Douglas, Michael G. Leith, Thomas C. Baddeley, John M. D. Storey, Gernot Riedel, Claude M. Wischik, Charles R. Harrington, Franz Theuring |
| Abstract |
α-Synuclein (α-Syn) aggregation is a pathological feature of synucleinopathies, neurodegenerative disorders that include Parkinson's disease (PD). We have tested whether N,N,N',N'-tetramethyl-10H-phenothiazine-3,7-diaminium bis(hydromethanesulfonate) (leuco-methylthioninium bis(hydromethanesulfonate); LMTM), a tau aggregation inhibitor, affects α-Syn aggregation in vitro and in vivo. Both cellular and transgenic models in which the expression of full-length human α-Syn (h-α-Syn) fused with a signal sequence peptide to promote α-Syn aggregation were used. Aggregated α-Syn was observed following differentiation of N1E-115 neuroblastoma cells transfected with h-α-Syn. The appearance of aggregated α-Syn was inhibited by LMTM, with an EC50 of 1.1 μM, with minimal effect on h-α-Syn mRNA levels being observed. Two independent lines of mice (L58 and L62) transgenic for the same fusion protein accumulated neuronal h-α-Syn that, with aging, developed into fibrillary inclusions characterized by both resistance to proteinase K (PK)-cleavage and their ability to bind thiazin red. There was a significant decrease in α-Syn-positive neurons in multiple brain regions following oral treatment of male and female mice with LMTM administered daily for 6 weeks at 5 and 15 mg MT/kg. The early aggregates of α-Syn and the late-stage fibrillar inclusions were both susceptible to inhibition by LMTM, a treatment that also resulted in the rescue of movement and anxiety-related traits in these mice. The results suggest that LMTM may provide a potential disease modification therapy in PD and other synucleinopathies through the inhibition of α-Syn aggregation. |
X Demographics
The data shown below were collected from the profiles of 3 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 | 33% |
| Switzerland | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 46 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 26% |
| Student > Master | 7 | 15% |
| Student > Bachelor | 6 | 13% |
| Professor | 2 | 4% |
| Lecturer | 1 | 2% |
| Other | 4 | 9% |
| Unknown | 14 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 9 | 20% |
| Agricultural and Biological Sciences | 4 | 9% |
| Chemistry | 4 | 9% |
| Medicine and Dentistry | 4 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 7% |
| Other | 6 | 13% |
| Unknown | 16 | 35% |
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 30 January 2018.
All research outputs
#14,373,275
of 23,016,919 outputs
Outputs from Frontiers in Molecular Neuroscience
#1,549
of 2,913 outputs
Outputs of similar age
#241,343
of 443,289 outputs
Outputs of similar age from Frontiers in Molecular Neuroscience
#57
of 118 outputs
Altmetric has tracked 23,016,919 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,913 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 43rd percentile – i.e., 43% 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 443,289 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 118 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.