Evidence map›Paper›PMID 33548223›Full record

ArticleThe Journal of biological chemistry

Spatiotemporal processing of neural cell adhesion molecules 1 and 2 by BACE1 in vivo.

WonHee Kim, Hiroto Watanabe, Selene Lomoio, Giuseppina Tesco

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Prospects and challenges in using neuronal extracellular vesicles in biomarker research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. BACE1: More than just a β-secretase.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022
    Review
  9. Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022
    Article
  10. Review
  11. Article
  12. Review
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

WonHee KimAlzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
Hiroto WatanabeAlzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
Selene LomoioAlzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
Giuseppina TescoAlzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA. Electronic address: Giuseppina.Tesco@Tufts.edu.
Tufts University · US

Funding

Role of BACE in the pathogenesis of Alzheimer's disease after head traumaR01NS092497 · NINDS · TUFTS UNIVERSITY BOSTON · PI TESCO, GIUSEPPINA · 2015 to 2018
$1.4M
NINDS NIH HHS R01 NS092497
6 · The paper itself

Abstract

Neural cell adhesion molecules 1 (NCAM1) and 2 (NCAM2) belong to the cell adhesion molecules of the immunoglobulin superfamily and have been shown to regulate formation, maturation, and maintenance of synapses. NCAM1 and NCAM2 undergo proteolysis, but the identity of all the proteases involved and how proteolysis is used to regulate their functions are not known. We report here that NCAM1 and NCAM2 are BACE1 substrates in vivo. NCAM1 and NCAM2 overexpressed in HEK cells were both cleaved by metalloproteinases or BACE1, and NCAM2 was also processed by γ-secretase. We identified the BACE1 cleavage site of NCAM1 (at Glu 671) and NCAM2 (at Glu 663) using mass spectrometry and site-directed mutagenesis. Next, we assessed BACE1-mediated processing of NCAM1 and NCAM2 in the mouse brain during aging. NCAM1 and NCAM2 were cleaved in the olfactory bulb of BACE1+/+ but not BACE1-/- mice at postnatal day 10 (P10), 4 and 12 months of age. In the hippocampus, a BACE1-specific soluble fragment of NCAM1 (sNCAM1β) was only detected at P10. However, we observed an accumulation of full-length NCAM1 in hippocampal synaptosomes in 4-month-old BACE1-/- mice. We also found that polysialylated NCAM1 (PSA-NCAM1) levels were increased in BACE1-/- mice at P10 and demonstrated that BACE1 cleaves both NCAM1 and PSA-NCAM1 in vitro. In contrast, we did not find evidence for BACE1-dependent NCAM2 processing in the hippocampus at any age analyzed. In summary, our data demonstrate that BACE1 differentially processes NCAM1 and NCAM2 depending on the region of brain, subcellular localization, and age in vivo.

Indexed as

Amyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesBrainCD56 AntigenCell Adhesion MoleculesFemaleHippocampusHumansMaleMiceMice, Inbred C57BLMice, KnockoutNeural Cell Adhesion Molecule L1Neural Cell Adhesion MoleculesNeuronsAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humanBace1 protein, mouseCD56 AntigenCell Adhesion MoleculesNCAM1 protein, humanNCAM2 protein, humanNcam2 protein, mouseNeural Cell Adhesion Molecule L1Neural Cell Adhesion Moleculespolysialic acidSialic AcidsBACE1neural cell adhesion molecule 1 (NCAM1)neural cell adhesion molecule 2 (NCAM2)polysialic acid (PSA)substratesynaptosomeβ-secretase

Identifiers

PMID33548223
PMCPMC7949136
OpenAlexW3128296246

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.