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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 (#44 of 1,464)
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (92nd percentile)

Citations

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105 Dimensions

Readers on

mendeley
142 Mendeley
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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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 142 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%
United Kingdom 1 <1%
United States 1 <1%
Unknown 135 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 35 25%
Researcher 33 23%
Student > Master 25 18%
Student > Bachelor 13 9%
Student > Doctoral Student 7 5%
Other 29 20%
Readers by discipline Count As %
Agricultural and Biological Sciences 41 29%
Medicine and Dentistry 23 16%
Biochemistry, Genetics and Molecular Biology 22 15%
Chemistry 19 13%
Neuroscience 16 11%
Other 21 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 41. 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 13 February 2018.
All research outputs
#311,473
of 11,598,144 outputs
Outputs from Acta Neuropathologica
#44
of 1,464 outputs
Outputs of similar age
#3,836
of 132,210 outputs
Outputs of similar age from Acta Neuropathologica
#1
of 14 outputs
Altmetric has tracked 11,598,144 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,464 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has done particularly well, scoring higher than 96% 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 132,210 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 97% of its contemporaries.
We're also able to compare this research output to 14 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.