Planar cell polarity signaling components are a direct target of β-amyloid-associated degeneration of glutamatergic synapses
| العنوان: | Planar cell polarity signaling components are a direct target of β-amyloid-associated degeneration of glutamatergic synapses |
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| المؤلفون: | Yimin Zou, Akumbir S. Grewal, Andiara E. Freitas, Bo Feng, Lilach Gorodetski, Yeo Rang Lee, Jingyi Wang, Runyi Tian |
| المصدر: | Science advances, vol 7, iss 34 Science Advances |
| بيانات النشر: | eScholarship, University of California, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Aging, Regulator, Receptors, Cell Surface, Degeneration (medical), Neurodegenerative, Alzheimer's Disease, Synapse, Glutamatergic, Mice, Developmental Neuroscience, Alzheimer Disease, Conditional gene knockout, Receptors, Acquired Cognitive Impairment, Animals, 2.1 Biological and endogenous factors, Aetiology, Receptor, Wnt Signaling Pathway, Research Articles, Multidisciplinary, Amyloid beta-Peptides, Chemistry, Wnt signaling pathway, Neurosciences, SciAdv r-articles, Receptor Protein-Tyrosine Kinases, Cell Polarity, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Cadherins, Brain Disorders, Synapses, Cell Surface, Neurological, Dementia, Signal transduction, Neuroscience, Research Article, Biotechnology |
| الوصف: | Amyloid beta oligomers cause glutamatergic synapse degeneration by targeting the planar cell polarity components in the synapses. The signaling pathway directly controlling the maintenance of adult glutamatergic synapses has not been well understood. Planar cell polarity (PCP) signaling components were recently shown to play essential roles in the formation of glutamatergic synapses. Here, we show that they are localized in the adult synapses and are essential for their maintenance. Synapse loss at early stages of Alzheimer’s disease is thought to be induced by β-amyloid (Aβ) pathology. We found that oligomeric Aβ binds to Celsr3 and assists Vangl2 in disassembling synapses. Moreover, a Wnt receptor and regulator of PCP signaling, Ryk, is also required for Aβ-induced synapse loss. In the 5XFAD mouse model of Alzheimer’s disease, Ryk conditional knockout or a function-blocking monoclonal Ryk antibody protected synapses and preserved cognitive function. We propose that tipping of the fine balance of Wnt/PCP signaling components in glutamatergic synapses may cause synapse degeneration in neurodegenerative disorders with Aβ pathology. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a46919abbb65573b23a97ed30b5def2 https://escholarship.org/uc/item/5kx8h77b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8a46919abbb65573b23a97ed30b5def2 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |