ArticlePloS one2014
Extracellular proteolysis of apolipoprotein E (apoE) by secreted serine neuronal protease.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
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.
Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Validation of human kallikrein 6 in the cerebrospinal fluid of patients with progressive and non-progressive alzheimer's disease: correlation with other biomarkers.Clinical proteomics · 2026Article
- ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer's Disease Pathogenesis.Biochemistry · 2025Article
- Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases.Aging and disease · 2023Review
- Exercise modulates APOE expression in brain cortex of female APOE3 and APOE4 targeted replacement mice.Neuropeptides · 2023Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Remembering your A, B, C's: Alzheimer's disease and ABCA1.Acta pharmaceutica Sinica. B · 2022Review
- Are apolipoprotein E fragments a promising new therapeutic target for Alzheimer's disease?Therapeutic advances in chronic disease · 2022Review
- Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation.Glia · 2021Article
- Astrocytic and Neuronal Apolipoprotein E Isoforms Differentially Affect Neuronal Excitability.Frontiers in neuroscience · 2021Article
- Alzheimer's disease pathology in APOE transgenic mouse models: The Who, What, When, Where, Why, and How.Neurobiology of disease · 2020Review
- Using human induced pluripotent stem cells (hiPSCs) to investigate the mechanisms by which Apolipoprotein E (APOE) contributes to Alzheimer's disease (AD) risk.Neurobiology of disease · 2020Review
- Understanding the Role of ApoE Fragments in Alzheimer's Disease.Neurochemical research · 2019Review
- Phagocytosis of Apoptotic Cells Is Specifically Upregulated in ApoE4 Expressing MicrogliaFrontiers in cellular neuroscience · 2019Article
- APOE hypermethylation is associated with autism spectrum disorder in a Chinese population.Experimental and therapeutic medicine · 2018Article
- The serine protease HtrA1 contributes to the formation of an extracellular 25-kDa apolipoprotein E fragment that stimulates neuritogenesis.The Journal of biological chemistry · 2018Article
- Assessment of kallikrein 6 as a cross-sectional and longitudinal biomarker for Alzheimer's disease.Alzheimer's research & therapy · 2018Article
- Molecular Mechanisms of the R61T Mutation in Apolipoprotein E4: A Dynamic Rescue.Biophysical journal · 2017Article
- Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease.Current opinion in lipidology · 2017Review
- HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective.Journal of the American Chemical Society · 2016Article
- The Effect of the APOE4 Gene on Accumulation of Aβ40 After Brain Injury Cannot Be Reversed by Increasing apoE4 Protein.Journal of neuropathology and experimental neurology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Under normal conditions, brain apolipoprotein E (apoE) is secreted and lipidated by astrocytes, then taken up by neurons via receptor mediated endocytosis. Free apoE is either degraded in intraneuronal lysosomal compartments or released. Here we identified a novel way by which apoE undergoes proteolysis in the extracellular space via a secreted neuronal protease. We show that apoE is cleaved in neuronal conditioned media by a secreted serine protease. This apoE cleavage was inhibited by PMSF and α1-antichymotrypsin, but not neuroserpin-1 or inhibitors of thrombin and cathepsin G, supporting its identity as a chymotrypsin like protease. In addition, apoE incubation with purified chymotrypsin produced a similar pattern of apoE fragments. Analysis of apoE fragments by mass spectrometry showed cleavages occurring at the C-terminal side of apoE tryptophan residues, further supporting our identification of cleavage by chymotrypsin like protease. Hippocampal neurons were more efficient in mediating this apoE cleavage than cortical neurons. Proteolysis of apoE4 generated higher levels of low molecular weight fragments compared to apoE3. Primary glial cultures released an inhibitor of this proteolytic activity. Together, these studies reveal novel mechanism by which apoE can be regulated and therefore could be useful in designing apoE directed AD therapeutic approaches.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.