ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
A death receptor 6-amyloid precursor protein pathway regulates synapse density in the mature CNS but does not contribute to Alzheimer's disease-related pathophysiology in murine models.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- The Intricate Role of Caspase-6 and Death Receptor-6 in Neurodegenerative Diseases.Cell biochemistry and biophysics · 2026Review
- Blood-brain barrier dysfunction and peripheral immune activation in Alzheimer's disease: an inflammation-centered review.Frontiers in immunology · 2026Review
- Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.Pharmaceutics · 2025Review
- Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Molecular signatures in prion disease: altered death receptor pathways in a mouse model.Journal of translational medicine · 2024Article
- Endothelial DR6 in blood-brain barrier malfunction in Alzheimer's disease.Cell death & disease · 2024Article
- Insights on the Use of Transgenic Mice Models in Alzheimer's Disease Research.International journal of molecular sciences · 2024Review
- Pomegranate: A Source of Multifunctional Bioactive Compounds Potentially Beneficial in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow.Nature communications · 2020Article
- Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Proapoptotic Mitochondrial Carrier Homolog Protein PSAP Mediates Death Receptor 6 Induced Apoptosis.Journal of Alzheimer's disease : JAD · 2020Article
- Characterization of the selective in vitro and in vivo binding properties of crenezumab to oligomeric Aβ.Alzheimer's research & therapy · 2019Article
- p75NTR and DR6 Regulate Distinct Phases of Axon Degeneration Demarcated by Spheroid Rupture.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Emerging Alternative Proteinases in APP Metabolism and Alzheimer's Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP.Frontiers in aging neuroscience · 2019Review
- A Role forFrontiers in cellular neuroscience · 2019Article
- Physiological functions of non-apoptotic caspase activity in the nervous system.Seminars in cell & developmental biology · 2018Review
- Unique Sensory and Motor Behavior in Thy1-GFP-M Mice before and after Spinal Cord Injury.Journal of neurotrauma · 2018Article
- Non-cell-autonomous function of DR6 in Schwann cell proliferation.The EMBO journal · 2018Article
- Neuronal Cell Death.Physiological reviews · 2018Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies implicate death receptor 6 (DR6) in an amyloid precursor protein (APP)-dependent pathway regulating developmental axon pruning, and in a pruning pathway operating during plastic rearrangements in adult brain. DR6 has also been suggested to mediate toxicity in vitro of Aβ peptides derived from APP. Given the link between APP, Aβ, and Alzheimer's disease (AD), these findings have raised the possibility that DR6 contributes to aspects of neurodegeneration in AD. To test this possibility, we have used mouse models to characterize potential function(s) of DR6 in the adult CNS and in AD-related pathophysiology. We show that DR6 is broadly expressed within the adult CNS and regulates the density of excitatory synaptic connections onto pyramidal neurons in a genetic pathway with APP. DR6 knock-out also gives rise to behavioral abnormalities, some of which are similar to those previously documented in APP knock-out animals. However, in two distinct APP transgenic models of AD, we did not observe any alteration in the formation of amyloid plaques, gliosis, synaptic loss, or cognitive behavioral deficits with genetic deletion of DR6, though we did observe a transient reduction in the degree of microglial activation in one model. Our results support the view that DR6 functions with APP to modulate synaptic density in the adult CNS, but do not provide evidence for a role of DR6 in the pathophysiology of AD.
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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.