ArticlePloS one2016
Cystatin C Shifts APP Processing from Amyloid-β Production towards Non-Amyloidgenic Pathway in Brain Endothelial Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Cystatin C and its Role in the Neuro-Glial-Vascular Unit: Implications for Cerebrovascular Diseases and Neurodegeneration.Neuroscience bulletin · 2026Review
- Unravelling the Significance of Cystatin C and Bunina Bodies in Amyotrophic Lateral Sclerosis Pathogenesis.Neuropathology and applied neurobiology · 2026Review
- Expression and function of β-site amyloid precursor protein-cleaving enzyme 2 in vascular endothelium.American journal of physiology. Heart and circulatory physiology · 2025Article
- From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Cerebrovascular Endothelial Dysfunction: Role of BACE1.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Human cystatin C induces the disaggregation process of selected amyloid beta peptides: a structural and kinetic view.Scientific reports · 2023Article
- Loss of cystatin C regulates permeability and inflammatory pathways in retina.Microvascular research · 2023Article
- Impact of Serum Cystatin C Level on Long-Term Cognitive Impairment After Acute Ischemic Stroke and Transient Ischemic Attack.Neuropsychiatric disease and treatment · 2023Article
- Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells.International journal of molecular sciences · 2021Article
- Review
- Soluble Expression of Recombinant Human Cystatin C and Comparison of the Ni Column and Magnetic Bead Purification.The protein journal · 2020Article
- Caspr1 Facilitates sAPPα Production by Regulating α-Secretase ADAM9 in Brain Endothelial Cells.Frontiers in molecular neuroscience · 2020Article
- Procyanidins and Alzheimer's Disease.Molecular neurobiology · 2019Review
- Sirtuins in Alzheimer's Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics.International journal of molecular sciences · 2019Article
- Alpha-synuclein alters differently gene expression of Sirts, PARPs and other stress response proteins: implications for neurodegenerative disorders.Molecular neurobiology · 2018Article
- A mechanistic model to predict effects of cathepsin B and cystatin C on β-amyloid aggregation and degradation.The Journal of biological chemistry · 2017Article
- Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations.Frontiers in physiology · 2017Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid-β (Aβ), the major component of neuritic plaques in Alzheimer's disease (AD), is derived from sequential proteolytic cleavage of amyloid protein precursor (APP) by secretases. In this study, we found that cystatin C (CysC), a natural cysteine protease inhibitor, is able to reduce Aβ40 secretion in human brain microvascular endothelial cells (HBMEC). The CysC-induced Aβ40 reduction was caused by degradation of β-secretase BACE1 through the ubiquitin/proteasome pathway. In contrast, we found that CysC promoted secretion of soluble APPα indicating the activated non-amyloidogenic processing of APP in HBMEC. Further results revealed that α-secretase ADAM10, which was transcriptionally upregulated in response to CysC, was required for the CysC-induced sAPPα secretion. Knockdown of SIRT1 abolished CysC-triggered ADAM10 upregulation and sAPPα production. Taken together, our results demonstrated that exogenously applied CysC can direct amyloidogenic APP processing to non-amyloidgenic pathway in brain endothelial cells, mediated by proteasomal degradation of BACE1 and SIRT1-mediated ADAM10 upregulation. Our study unveils previously unrecognized protective role of CysC in APP processing.
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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.