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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Modifying Rap1-signalling by targeting Pde6δ is neuroprotective in models of Alzheimer’s disease
|
|---|---|
| Published in |
Molecular Neurodegeneration, September 2018
|
| DOI | 10.1186/s13024-018-0283-3 |
| Pubmed ID | |
| Authors |
Michael Dumbacher, Tom Van Dooren, Katrien Princen, Koen De Witte, Mélissa Farinelli, Sam Lievens, Jan Tavernier, Wim Dehaen, Stefaan Wera, Joris Winderickx, Sara Allasia, Amuri Kilonda, Stéphane Spieser, Arnaud Marchand, Patrick Chaltin, Casper C. Hoogenraad, Gerard Griffioen |
| Abstract |
Neuronal Ca2+ dyshomeostasis and hyperactivity play a central role in Alzheimer's disease pathology and progression. Amyloid-beta together with non-genetic risk-factors of Alzheimer's disease contributes to increased Ca2+ influx and aberrant neuronal activity, which accelerates neurodegeneration in a feed-forward fashion. As such, identifying new targets and drugs to modulate excessive Ca2+ signalling and neuronal hyperactivity, without overly suppressing them, has promising therapeutic potential. Here we show, using biochemical, electrophysiological, imaging, and behavioural tools, that pharmacological modulation of Rap1 signalling by inhibiting its interaction with Pde6δ normalises disease associated Ca2+ aberrations and neuronal activity, conferring neuroprotection in models of Alzheimer's disease. The newly identified inhibitors of the Rap1-Pde6δ interaction counteract AD phenotypes, by reconfiguring Rap1 signalling underlying synaptic efficacy, Ca2+ influx, and neuronal repolarisation, without adverse effects in-cellulo or in-vivo. Thus, modulation of Rap1 by Pde6δ accommodates key mechanisms underlying neuronal activity, and therefore represents a promising new drug target for early or late intervention in neurodegenerative disorders. Targeting the Pde6δ-Rap1 interaction has promising therapeutic potential for disorders characterised by neuronal hyperactivity, such as Alzheimer's disease. |
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 States | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 2 | 67% |
| Members of the public | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 21% |
| Student > Bachelor | 2 | 8% |
| Student > Postgraduate | 2 | 8% |
| Student > Ph. D. Student | 2 | 8% |
| Professor | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 10 | 42% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 21% |
| Neuroscience | 2 | 8% |
| Medicine and Dentistry | 2 | 8% |
| Agricultural and Biological Sciences | 2 | 8% |
| Unspecified | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 10 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. 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 09 October 2018.
All research outputs
#2,801,864
of 23,103,903 outputs
Outputs from Molecular Neurodegeneration
#374
of 858 outputs
Outputs of similar age
#59,682
of 341,556 outputs
Outputs of similar age from Molecular Neurodegeneration
#10
of 17 outputs
Altmetric has tracked 23,103,903 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 858 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.4. This one has gotten more attention than average, scoring higher than 56% 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 341,556 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 82% of its contemporaries.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.