Evidence map›Paper›PMID 22434822›Full record

ArticleHuman molecular genetics2012

Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates Aβ production.

Alessio Vagnoni, Michael S Perkinton, Emma H Gray, Paul T Francis, Wendy Noble, Christopher C J Miller

Open access · hybridAbstract read
In one paragraph

Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% 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

86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.

  1. Pooled it
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  4. Article
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26 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Alessio VagnoniKCL Centre for Neurodegeneration Research, Department of Neuroscience, Institute of Psychiatry, King’s College London, De Crespigny Park, London, UK
Michael S Perkinton
Emma H Gray
Paul T Francis
Wendy Noble
Christopher C J Miller
Neuroscience Institute · ITKing's College London · GB

Funding

Medical Research Council G0501573Wellcome Trust 078662
6 · The paper itself

Abstract

Understanding the mechanisms that control processing of the amyloid precursor protein (APP) to produce amyloid-β (Aβ) peptide represents a key area of Alzheimer's disease research. Here, we show that siRNA-mediated loss of calsyntenin-1 in cultured neurons alters APP processing to increase production of Aβ. We also show that calsyntenin-1 is reduced in Alzheimer's disease brains and that the extent of this reduction correlates with increased Aβ levels. Calsyntenin-1 is a ligand for kinesin-1 light chains and APP is transported through axons on kinesin-1 molecular motors. Defects in axonal transport are an early pathological feature in Alzheimer's disease and defective APP transport is known to increase Aβ production. We show that calsyntenin-1 and APP are co-transported through axons and that siRNA-induced loss of calsyntenin-1 markedly disrupts axonal transport of APP. Thus, perturbation to axonal transport of APP on calsyntenin-1 containing carriers induces alterations to APP processing that increase production of Aβ. Together, our findings suggest that disruption of calsyntenin-1-associated axonal transport of APP is a pathogenic mechanism in Alzheimer's disease.

Indexed as

Axonal TransportADAM10 ProteinADAM ProteinsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesAxonsCalcium-Binding ProteinsCells, CulturedGreen Fluorescent ProteinsKinesinsMembrane GlycoproteinsPresenilin-1ADAM10 ProteinADAM10 protein, ratADAM ProteinsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBace1 protein, ratCalcium-Binding ProteinsClstn1 protein, ratenhanced green fluorescent proteinGreen Fluorescent ProteinsKinesinsMembrane Glycoproteinsnicastrin proteinPresenilin-1RNA, Small Interfering

Identifiers

PMID22434822
PMCPMC3373235
OpenAlexW2103848039

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.