| Title |
Inhibition of γ-Secretase Leads to an Increase in Presenilin-1
|
|---|---|
| Published in |
Molecular Neurobiology, August 2017
|
| DOI | 10.1007/s12035-017-0705-1 |
| Pubmed ID | |
| Authors |
Aitana Sogorb-Esteve, María-Salud García-Ayllón, Marta Llansola, Vicente Felipo, Kaj Blennow, Javier Sáez-Valero |
| Abstract |
γ-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that γ-secretase inhibition can provoke a rebound effect, elevating the levels of the catalytic γ-secretase subunit, presenilin-1 (PS1). Acute treatment of SH-SY5Y cells with the GSI LY-374973 (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, DAPT) augments PS1, in parallel with increases in other γ-secretase subunits nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1, yet with no increase in messenger RNA expression. Over-expression of the C-terminal fragment (CTF) of APP, C99, also triggered an increase in PS1. Similar increases in PS1 were evident in primary neurons treated repeatedly (4 days) with DAPT or with the GSI BMS-708163 (avagacestat). Likewise, rats examined after 21 days administered with avagacestat (40 mg/kg/day) had more brain PS1. Sustained γ-secretase inhibition did not exert a long-term effect on PS1 activity, evident through the decrease in CTFs of APP and ApoER2. Prolonged avagacestat treatment of rats produced a subtle impairment in anxiety-like behavior. The rebound increase in PS1 in response to GSIs must be taken into consideration for future drug development. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Venezuela, Bolivarian Republic of | 1 | 25% |
| Spain | 1 | 25% |
| Australia | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 71 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 16 | 23% |
| Student > Ph. D. Student | 11 | 15% |
| Student > Bachelor | 7 | 10% |
| Student > Master | 7 | 10% |
| Professor > Associate Professor | 3 | 4% |
| Other | 8 | 11% |
| Unknown | 19 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 12 | 17% |
| Biochemistry, Genetics and Molecular Biology | 11 | 15% |
| Medicine and Dentistry | 6 | 8% |
| Chemistry | 4 | 6% |
| Agricultural and Biological Sciences | 3 | 4% |
| Other | 13 | 18% |
| Unknown | 22 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 8. 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 02 July 2020.
All research outputs
#3,842,414
of 23,083,773 outputs
Outputs from Molecular Neurobiology
#829
of 3,497 outputs
Outputs of similar age
#62,607
of 287,892 outputs
Outputs of similar age from Molecular Neurobiology
#4
of 77 outputs
Altmetric has tracked 23,083,773 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,497 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done well, scoring higher than 75% 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 287,892 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 77% of its contemporaries.
We're also able to compare this research output to 77 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 93% of its contemporaries.