ArticleCell death & disease2012
TRAIL death receptors DR4 and DR5 mediate cerebral microvascular endothelial cell apoptosis induced by oligomeric Alzheimer's Aβ.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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Who cites it
51 citing papers in PubMed, 78 citations in OpenAlex.
- Mitochondrial carbonic anhydrase-VB inhibition rescues brain endothelial stress and memory in Alzheimer's disease models.Science advances · 2026Article
- Genetic and epidemiological analyses of alcohol consumption patterns and age-related macular degeneration risk among current drinkers: a role for TNFRSF10A.Journal of global health · 2026Article
- The meningeal lymphatic vessel-peripheral immune axis: a novel therapeutic target in neurodegenerative diseases.Journal of neuroinflammation · 2026Review
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Amyloid β Instigates Cardiac Neurotrophic Signaling Impairment, Driving Alzheimer's Associated Heart Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Mitochondrial carbonic anhydrase-VB inhibition rescues brain endothelial stress and memory in Alzheimer's disease models.bioRxiv : the preprint server for biology · 2026Article
- Article
- Influence of Alzheimer's associated Aβ oligomers and oxidative stress on blood-brain barrier dysfunction.Tissue barriers · 2026Article
- Modulation of experimental Alzheimer's disease in rats through donepezil-loaded CSF implant.Scientific reports · 2025Article
- Cerebrospinal fluid proteomics for predictive assessment of Alzheimer's Disease risk.medRxiv : the preprint server for health sciences · 2025Article
- PANoptosis in cancer: molecular mechanisms and therapeutic potential.Cancer gene therapy · 2025Review
- Alterations in the inflammatory homeostasis of aging-related cardiac dysfunction and Alzheimer's diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Caspases in Alzheimer's Disease: Mechanism of Activation, Role, and Potential Treatment.Molecular neurobiology · 2024Review
- Homocysteine potentiates amyloidAging cell · 2024Article
- Review
- Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Article
- FDA-approved carbonic anhydrase inhibitors reduce amyloid β pathology and improve cognition, by ameliorating cerebrovascular health and glial fitness.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Vascular deposition of amyloid-β (Aβ) in sporadic and familial Alzheimer's disease, through poorly understood molecular mechanisms, leads to focal ischemia, alterations in cerebral blood flow, and cerebral micro-/macro-hemorrhages, significantly contributing to cognitive impairment. Here, we show that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors DR4 and DR5 specifically mediate oligomeric Aβ induction of extrinsic apoptotic pathways in human microvascular cerebral endothelial cells with activation of both caspase-8 and caspase-9. The caspase-8 inhibitor cellular FLICE-like inhibitory protein (cFLIP) is downregulated, and mitochondrial paths are engaged through BH3-interacting domain death agonist (Bid) cleavage. Upregulation of DR4 and DR5 and colocalization with Aβ at the cell membrane suggests their involvement as initiators of the apoptotic machinery. Direct binding assays using receptor chimeras confirm the specific interaction of oligomeric Aβ with DR4 and DR5 whereas apoptosis protection achieved through RNA silencing of both receptors highlights their active role in downstream apoptotic pathways unveiling new targets for therapeutic intervention.
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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.