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Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons

Overview of attention for article published in Molecular Neurodegeneration, October 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (76th percentile)
  • Average Attention Score compared to outputs of the same age and source

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1 news outlet

Citations

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83 Mendeley
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Title
Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons
Published in
Molecular Neurodegeneration, October 2016
DOI 10.1186/s13024-016-0134-z
Pubmed ID
Authors

Martina Pigoni, Johanna Wanngren, Peer-Hendrik Kuhn, Kathryn M. Munro, Jenny M. Gunnersen, Hiroshi Takeshima, Regina Feederle, Iryna Voytyuk, Bart De Strooper, Mikail D. Levasseur, Brian J. Hrupka, Stephan A. Müller, Stefan F. Lichtenthaler

Abstract

The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer's disease. However, BACE1 therapeutic inhibition may cause unwanted adverse effects due to its additional functions in the nervous system, such as in myelination and neuronal connectivity. Additionally, recent proteomic studies investigating BACE1 inhibition in cell lines and cultured murine neurons identified a wider range of neuronal membrane proteins as potential BACE1 substrates, including seizure protein 6 (SEZ6) and its homolog SEZ6L. We generated antibodies against SEZ6 and SEZ6L and validated these proteins as BACE1 substrates in vitro and in vivo. Levels of the soluble, BACE1-cleaved ectodomain of both proteins (sSEZ6, sSEZ6L) were strongly reduced upon BACE1 inhibition in primary neurons and also in vivo in brains of BACE1-deficient mice. BACE1 inhibition increased neuronal surface levels of SEZ6 and SEZ6L as shown by cell surface biotinylation, demonstrating that BACE1 controls surface expression of both proteins. Moreover, mass spectrometric analysis revealed that the BACE1 cleavage site in SEZ6 is located in close proximity to the membrane, similar to the corresponding cleavage site in SEZ6L. Finally, an improved method was developed for the proteomic analysis of murine cerebrospinal fluid (CSF) and was applied to CSF from BACE-deficient mice. Hereby, SEZ6 and SEZ6L were validated as BACE1 substrates in vivo by strongly reduced levels in the CSF of BACE1-deficient mice. This study demonstrates that SEZ6 and SEZ6L are physiological BACE1 substrates in the murine brain and suggests that sSEZ6 and sSEZ6L levels in CSF are suitable markers to monitor BACE1 inhibition in mice.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 83 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 19 23%
Researcher 12 14%
Student > Master 12 14%
Student > Ph. D. Student 10 12%
Student > Postgraduate 4 5%
Other 8 10%
Unknown 18 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 25%
Neuroscience 15 18%
Agricultural and Biological Sciences 10 12%
Medicine and Dentistry 4 5%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 9 11%
Unknown 21 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 29 October 2016.
All research outputs
#4,194,102
of 22,893,031 outputs
Outputs from Molecular Neurodegeneration
#512
of 851 outputs
Outputs of similar age
#70,117
of 319,503 outputs
Outputs of similar age from Molecular Neurodegeneration
#6
of 10 outputs
Altmetric has tracked 22,893,031 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 851 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.2. This one is in the 38th percentile – i.e., 38% 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 319,503 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 76% of its contemporaries.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.