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Characterisation of PDGF-BB:PDGFRβ signalling pathways in human brain pericytes: evidence of disruption in Alzheimer's disease.
- Source :
-
Communications Biology . 3/17/2022, Vol. 5 Issue 1, p1-16. 16p. - Publication Year :
- 2022
-
Abstract
- 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. Smyth et al. use tissue microarrays from Alzheimer's disease (AD) patient brains to show that PDGF-BB:PDGFRβ signalling components are reduced in AD. They then use primary human brain pericytes to elucidate a pathway by which PDGF-BB:PDGFRβ signalling in brain pericytes is disrupted in AD, thus impairing the blood brain barrier. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PERICYTES
*ALZHEIMER'S disease
*CELLULAR signal transduction
*BLOOD-brain barrier
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 5
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Communications Biology
- Publication Type :
- Academic Journal
- Accession number :
- 155873307
- Full Text :
- https://doi.org/10.1038/s42003-022-03180-8