#IDIBELLseminars: Unlocking the Brain’s Gatekeeper: LRP1/Syndapin-2 Pathway as a New Avenue for Therapy

The brain’s vasculature, with its selective endothelial cells, forms the blood-brain barrier (BBB), regulating molecular transport between the blood and central nervous system. Among BBB receptors, the low-density lipoprotein receptor-related protein 1 (LRP1) is key for clearing misfolded proteins and is linked to neurodegeneration. Our research shows that LRP1 interacts with syndapin-2 (Sy2) to support transcytosis and amyloid-β (Aβ) clearance, a process disrupted in Alzheimer’s disease (AD). We found that Sy2 enhances LRP1-mediated transport for mid-avidity cargos, while high-avidity cargos are prone to degradation. Sy2 levels decline with age and AD risk factors, impairing Aβ clearance. These findings highlight the LRP1/Sy2 pathway as vital for BBB integrity and a target for AD therapies. I will discuss LRP1’s structure, its trafficking within the BBB, and present a therapeutic approach integrating receptor modulation to restore LRP1/Sy2 activity in AD models, pioneering a new drug design paradigm.

Hosted by Antonella Consiglio – Stem cells and neurodegenerative diseases group

I am an ICREA Professor and lead the Molecular Bionics Group at the Institute for Bioengineering of Catalonia (IBEC). I am also Honorary Professor at University College London (UCL) and Visiting Professor at West China Hospital, Sichuan University. I hold a Laurea in Chemical Engineering (University of Palermo), and a PhD in Soft Matter Physics (University of Sheffield -UoS). Before moving to Barcelona, I held positions at UoS (Assist. Professor 2006-09, Assoc. Professor 2009-11, Full Professor 2011-13) and at UCL, where I was full professor from 2013 to 2021. My research bridges physics, chemistry, and biology to investigate molecular transport across biological barriers, aiming to develop therapies for dementia, cancer, and immune disorders. I have secured over €41 million in research funding from research councils, charity and industry. Finally I am the director and founder of Vianautis Bio ltd, a UK start up today employing 35+ people and developing novel genetic therapies.