So excited to share our first neuro focused paper from the lab, we show that CXCL4 (PF4) is transported into the brain by proteoglycans within the endothelial glycocalyx and that GAG binding also mediates the pro neurogenesis effects of CXCL4. www.biorxiv.org/content/10.1... - ThreadSky

douglaspdyer.bsky.social • 22 days ago

So excited to share our first neuro focused paper from the lab, we show that CXCL4 (PF4) is transported into the brain by proteoglycans within the endothelial glycocalyx and that GAG binding also mediates the pro neurogenesis effects of CXCL4. https://www.biorxiv.org/content/10.1101/2025.04.23.650173v1

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groomlab.bsky.social•11 days ago

Congratulations Doug and team

douglaspdyer.bsky.social•11 days ago

Thanks Jo!

doctoremmerson.bsky.social•11 days ago

Congratulations Doug and team! Looking forward to reading this.

douglaspdyer.bsky.social•22 days ago

@gjbrainresearch.bsky.social

douglaspdyer.bsky.social•22 days ago

#Immunosky 🧪

douglaspdyer.bsky.social•22 days ago

building on work from others that CXCL4 has anti-ageing effects on the brain and our work that’s its receptors are proetoglycans within the goycocalyx. https://pubmed.ncbi.nlm.nih.gov/36640356/

douglaspdyer.bsky.social•22 days ago

We firstly showed that mouse CXCL4 behaves like the human version with a high affinity interaction with he GAG sugar side chains of proteoglycans, crucially with the slow off rate that we previously demonstrated drives GAG cross-linking and signaling. https://royalsocietypublishing.org/doi/full/10.1098/rsob.160286

douglaspdyer.bsky.social•22 days ago

We next investigated CXCL4 movement into the brain, firstly showing it can bind to GAGs on endothelial cells and used radio labeled tracer studies to show it can be enter the brain parenchyma in a GAG dependent fashion.

douglaspdyer.bsky.social•22 days ago

We then used in situ radio labeled studies to show CXCL4 and its mutant that doesn’t cross link GAG chains are rapidly cleared from the circulation and enter the brain. Surprisingly the mutant entered quicker due to its rapid dynamics allowing quicker release from the transporting proteoglycans.

douglaspdyer.bsky.social•22 days ago

To test this hypothesis we analysed wild type and mutant presence in vascular and parenchymal brain fractions, as hypothesised the WT was retained longer in the vasculature than the mutant, potentially enabling local signaling.

douglaspdyer.bsky.social•22 days ago

To confirm entry we used our cranial window imaging approach to analyse movement of fluorescent labelled CXCL4, showing entry into the brain, interaction with the vascular and excitingly potential interaction with neuronal structures…

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