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Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease.

Overview of attention for article published in Acta Neuropathologica, April 2013
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#39 of 964)
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (92nd percentile)

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mendeley
125 Mendeley
citeulike
1 CiteULike
Title
Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease.
Published in
Acta Neuropathologica, April 2013
DOI 10.1007/s00401-013-1114-9
Pubmed ID
Authors

Jens Wagner, Sergey Ryazanov, Andrei Leonov, Johannes Levin, Song Shi, Felix Schmidt, Catharina Prix, Francisco Pan-Montojo, Uwe Bertsch, Gerda Mitteregger-Kretzschmar, Markus Geissen, Martin Eiden, Fabienne Leidel, Thomas Hirschberger, Andreas A. Deeg, Julian J. Krauth, Wolfgang Zinth, Paul Tavan, Jens Pilger, Markus Zweckstetter, Tobias Frank, Mathias Bähr, Jochen H. Weishaupt, Manfred Uhr, Henning Urlaub, Ulrike Teichmann, Matthias Samwer, Kai Bötzel, Martin Groschup, Hans Kretzschmar, Christian Griesinger, Armin Giese, Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F, Prix C, Pan-Montojo F, Bertsch U, Mitteregger-Kretzschmar G, Geissen M, Eiden M, Leidel F, Hirschberger T, Deeg AA, Krauth JJ, Zinth W, Tavan P, Pilger J, Zweckstetter M, Frank T, Bähr M, Weishaupt JH, Uhr M, Urlaub H, Teichmann U, Samwer M, Bötzel K, Groschup M, Kretzschmar H, Griesinger C, Giese A, Mathias Bähr, Kai Bötzel

Abstract

In neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and prion diseases, deposits of aggregated disease-specific proteins are found. Oligomeric aggregates are presumed to be the key neurotoxic agent. Here we describe the novel oligomer modulator anle138b [3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole], an aggregation inhibitor we developed based on a systematic high-throughput screening campaign combined with medicinal chemistry optimization. In vitro, anle138b blocked the formation of pathological aggregates of prion protein (PrP(Sc)) and of α-synuclein (α-syn), which is deposited in PD and other synucleinopathies such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Notably, anle138b strongly inhibited all prion strains tested including BSE-derived and human prions. Anle138b showed structure-dependent binding to pathological aggregates and strongly inhibited formation of pathological oligomers in vitro and in vivo both for prion protein and α-synuclein. Both in mouse models of prion disease and in three different PD mouse models, anle138b strongly inhibited oligomer accumulation, neuronal degeneration, and disease progression in vivo. Anle138b had no detectable toxicity at therapeutic doses and an excellent oral bioavailability and blood-brain-barrier penetration. Our findings indicate that oligomer modulators provide a new approach for disease-modifying therapy in these diseases, for which only symptomatic treatment is available so far. Moreover, our findings suggest that pathological oligomers in neurodegenerative diseases share structural features, although the main protein component is disease-specific, indicating that compounds such as anle138b that modulate oligomer formation by targeting structure-dependent epitopes can have a broad spectrum of activity in the treatment of different protein aggregation diseases.

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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 %
Germany 4 3%
Russian Federation 1 <1%
France 1 <1%
United Kingdom 1 <1%
United States 1 <1%
Unknown 117 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 31 25%
Researcher 31 25%
Student > Master 23 18%
Student > Bachelor 10 8%
Student > Doctoral Student 7 6%
Other 23 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 43 34%
Medicine and Dentistry 21 17%
Biochemistry, Genetics and Molecular Biology 17 14%
Chemistry 17 14%
Neuroscience 11 9%
Other 16 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 39. 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 15 December 2017.
All research outputs
#273,308
of 8,907,341 outputs
Outputs from Acta Neuropathologica
#39
of 964 outputs
Outputs of similar age
#3,826
of 120,423 outputs
Outputs of similar age from Acta Neuropathologica
#1
of 13 outputs
Altmetric has tracked 8,907,341 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 964 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.7. This one has done particularly well, scoring higher than 95% 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 120,423 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 13 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 92% of its contemporaries.