| Autor: |
Leon C. D. Smyth, Blake Highet, Deidre Jansson, Jane Wu, Justin Rustenhoven, Miranda Aalderink, Adelie Tan, Susan Li, Rebecca Johnson, Natacha Coppieters, Renee Handley, Pritika Narayan, Malvindar K. Singh-Bains, Patrick Schweder, Clinton Turner, Edward W. Mee, Peter Heppner, Jason Correia, Thomas I.-H. Park, Maurice A. Curtis, Richard L. M. Faull, Mike Dragunow |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Communications biology. 5(1) |
| ISSN: |
2399-3642 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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