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Characterisation of PDGF-BB:PDGFRß signalling pathways in human brain pericytes: evidence of disruption in Alzheimer's disease.
Smyth, Leon C D; Highet, Blake; Jansson, Deidre; Wu, Jane; Rustenhoven, Justin; Aalderink, Miranda; Tan, Adelie; Li, Susan; Johnson, Rebecca; Coppieters, 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.
Affiliation
  • Smyth LCD; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
  • Highet B; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Jansson D; Centre for Free Radical Research, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
  • Wu J; Center for Brain Immunology and Glia, Department of Pathology and Immunology, Washington University in St Louis, Missouri, USA.
  • Rustenhoven J; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Aalderink M; Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.
  • Tan A; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
  • Li S; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Johnson R; Department of Psychiatry and Behavioural Sciences, University of Washington, Seattle, Washington, USA.
  • Coppieters N; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Handley R; Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.
  • Narayan P; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
  • Singh-Bains MK; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Schweder P; Center for Brain Immunology and Glia, Department of Pathology and Immunology, Washington University in St Louis, Missouri, USA.
  • Turner C; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
  • Mee EW; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Heppner P; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Correia J; Department of Anatomy with Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Auckland, 1023, New Zealand.
  • Park TI; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
  • Curtis MA; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Faull RLM; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
  • Dragunow M; Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Commun Biol ; 5(1): 235, 2022 03 17.
Article in En | MEDLINE | ID: mdl-35301433
Platelet-derived growth factor-BB (PDGF-BB):PDGF receptor-ß (PDGFRß) 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:PDGFRß signalling components were altered in human AD brains, with a marked reduction in vascular PDGFB. We hypothesised that reduced PDGF-BB:PDGFRß 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:PDGFRß signalling through Akt augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB signalling to stabilise the cerebrovasculature in AD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pericytes / Alzheimer Disease Limits: Humans Language: En Journal: Commun Biol Year: 2022 Document type: Article Affiliation country: New Zealand Country of publication: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pericytes / Alzheimer Disease Limits: Humans Language: En Journal: Commun Biol Year: 2022 Document type: Article Affiliation country: New Zealand Country of publication: United kingdom