ArticleEMBO molecular medicine2012
β-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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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.
The trial behind it
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Who cites it
76 citing papers in PubMed, 137 citations in OpenAlex.
- The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.EMBO molecular medicine · 2018Trial
- The Effects of Coenzyme Q10 Supplementation on the Contrast Sensitivity Score, Biomarkers of Oxidative Stress, Inflammation, and β-Secretase Activity in the Blood and the Correlation Among these Factors in Diabetic Retinopathy Patients; Clinical Trial.Advanced pharmaceutical bulletin · 2026Article
- Review
- VEGFR1 as a Target for Cardiovascular Gene Therapy.Journal of cardiovascular translational research · 2025Review
- Bacopa monnieri phytochemicals as promising BACE1 inhibitors for Alzheimer's disease therapy.Scientific reports · 2025Article
- Is the Relationship Between Cardiovascular Disease and Alzheimer's Disease Genetic? A Scoping Review.Genes · 2024Article
- Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications.Angiogenesis · 2024Review
- International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of Nonrodent Ocular Tissues.Toxicologic pathology · 2024Review
- The alteration and role of glycoconjugates in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- BACE1 in PV interneuron tunes hippocampal CA1 local circuits and resets priming of fear memory extinction.Molecular psychiatry · 2023Article
- siRNA drug delivery across the blood-brain barrier in Alzheimer's disease.Advanced drug delivery reviews · 2023Review
- β-secretase 1 overexpression by AAV-mediated gene delivery prevents retina degeneration in a mouse model of age-related macular degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- An Exploratory Study Provides Insights into MMP9 and Aβ Levels in the Vitreous and Blood across Different Ages and in a Subset of AMD Patients.International journal of molecular sciences · 2022Article
- Discovery and Characterization of Potent, Efficacious, Orally Available Antimalarial Plasmepsin X Inhibitors and Preclinical Safety Assessment ofJournal of medicinal chemistry · 2022Article
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model.EMBO molecular medicine · 2022Article
- Selected Natural Products in Neuroprotective Strategies for Alzheimer's Disease-A Non-Systematic Review.International journal of molecular sciences · 2022Review
- Cathepsin L and acute ischemic stroke: A mini-review.Frontiers in stroke · 2022Review
- The Emerging Roles of the β-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer.Frontiers in aging neuroscience · 2022Review
- The case for low-level BACE1 inhibition for the prevention of Alzheimer disease.Nature reviews. Neurology · 2021Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
β-Secretase (BACE1) is a major drug target for combating Alzheimer's disease (AD). Here we show that BACE1(-/-) mice develop significant retinal pathology including retinal thinning, apoptosis, reduced retinal vascular density and an increase in the age pigment, lipofuscin. BACE1 expression is highest in the neural retina while BACE2 was greatest in the retinal pigment epithelium (RPE)/choroid. Pigment epithelial-derived factor, a known regulator of γ-secretase, inhibits vascular endothelial growth factor (VEGF)-induced in vitro and in vivo angiogenesis and this is abolished by BACE1 inhibition. Moreover, intravitreal administration of BACE1 inhibitor or BACE1 small interfering RNA (siRNA) increases choroidal neovascularization in mice. BACE1 induces ectodomain shedding of vascular endothelial growth factor receptor 1 (VEGFR1) which is a prerequisite for γ-secretase release of a 100 kDa intracellular domain. The increase in lipofuscin following BACE1 inhibition and RNAI knockdown is associated with lysosomal perturbations. Taken together, our data show that BACE1 plays a critical role in retinal homeostasis and that the use of BACE inhibitors for AD should be viewed with extreme caution as they could lead to retinal pathology and exacerbate conditions such as age-related macular degeneration.
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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.