دورية أكاديمية
Characterisation of PDGF-BB:PDGFRβ signalling pathways in human brain pericytes: evidence of disruption in Alzheimer's disease.
| العنوان: | Characterisation of PDGF-BB:PDGFRβ signalling pathways in human brain pericytes: evidence of disruption in Alzheimer's disease. |
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| المؤلفون: | Smyth, Leon C D, Highet, Blake, Jansson, Deidre, Wu, Jane, Rustenhoven, Justin, Aalderink, Miranda, Tan, Adelie, Li, Susan, Johnson, Rebecca, Coppieters't Wallant, Natacha, Handley, Renee, Narayan, Pritika, Singh-Bains, Malvindar K, Schweder, Patrick, Turner, Clinton, Mee, Edward W, Heppner, Peter, Correia, Jason, Park, Thomas I-H, Curtis, Maurice A, Faull, Richard L M, Dragunow, Mike |
| المصدر: | Communications Biology, 5 (1), 235 (2022) |
| بيانات النشر: | Nature Research, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Becaplermin, Receptor, Platelet-Derived Growth Factor beta, Becaplermin/metabolism, Becaplermin/pharmacology, Brain/metabolism, Humans, Receptor, Platelet-Derived Growth Factor beta/metabolism, Receptor, Platelet-Derived Growth Factor beta/pharmacology, Alzheimer Disease/metabolism, Pericytes, Alzheimer Disease, Brain, Medicine (miscellaneous), Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Human health sciences, Neurology, Sciences de la santé humaine, Neurologie |
| الوصف: | Platelet-derived growth factor-BB (PDGF-BB):PDGF receptor-β (PDGFRβ) signalling in brain pericytes is critical to the development, maintenance and function of a healthy blood-brain barrier (BBB). Furthermore, BBB impairment and pericyte loss in Alzheimer's disease (AD) is well documented. We found that PDGF-BB:PDGFRβ signalling components were altered in human AD brains, with a marked reduction in vascular PDGFB. We hypothesised that reduced PDGF-BB:PDGFRβ signalling in pericytes may impact on the BBB. We therefore tested the effects of PDGF-BB on primary human brain pericytes in vitro to define pathways related to BBB function. Using pharmacological inhibitors, we dissected distinct aspects of the PDGF-BB response that are controlled by extracellular signal-regulated kinase (ERK) and Akt pathways. PDGF-BB promotes the proliferation of pericytes and protection from apoptosis through ERK signalling. In contrast, PDGF-BB:PDGFRβ signalling through Akt augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB signalling to stabilise the cerebrovasculature in AD. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article |
| اللغة: | English |
| Relation: | https://www.nature.com/articles/s42003-022-03180-8.pdf; urn:issn:2399-3642 |
| DOI: | 10.1038/s42003-022-03180-8 |
| URL الوصول: | https://orbi.uliege.be/handle/2268/293774 |
| حقوق: | open access http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess |
| رقم الأكسشن: | edsorb.293774 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1038/s42003-022-03180-8 |
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