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Unlocking the neurovascular interface of peripheral nerves in homeostasis, disease and repair

Project description

Exploring the neurovascular niche to understand and treat peripheral nervous system disorders

The peripheral nervous system (PNS) develops alongside the vascular system, creating a neurovascular (NV) interface that protects neural tissue through a blood-nerve barrier (BNB), similar to the blood-brain barrier. However, our understanding of the BNB is limited. The ERC-funded MINerVA project aims to investigate the NV interface of peripheral nerves, focusing on the role of endothelial cells and perivascular cells in maintaining BNB homeostasis and supporting recovery following injury and neuropathic pain. The project will map the NV niche, explore the impact of mechanobiology on the BNB through assays and mouse models, and develop molecular tools to probe and target the BNB. This study will pave the way for improved treatments for PNS disorders characterised by NV dysfunction.

Objective

"The extensive network of peripheral nerves develops concurrently and in close contact with the vascular system. This spatial and functional relationship persists into adulthood, forming a neurovascular (NV) interface that shields the vulnerable neural tissue through a blood-nerve barrier (BNB), akin to the blood-brain barrier (BBB). Despite its pivotal role in peripheral nervous system (PNS) health, our understanding of the BNB is limited, impacting the design of therapies for PNS disorders linked to vascular dysfunction. Our interdisciplinary proposal aims to define the molecular, cellular, and biomechanical features of the neurovascular interface of peripheral nerves. We hypothesize that vascular cells within this neurovascular interface are crucial for maintaining BNB homeostasis and for promoting the unique regenerative capacity of the PNS after injury. To accomplish our objectives, we have adopted a cross-disciplinary, innovative and synergistic approach. We will map the nerve vascular niche using advanced transcriptomic and proteomic approaches. Taking an original angle, we will explore the impact of mechanobiology on BNB homeostasis and the vascular response to damage by designing screening assays and mouse models to discover mechanotransduction systems operating in the nerve endothelium. Using agnostic in vivo peptide phage display technology, we will map unique ""ZIP codes"" on the nerve vasculature, enabling selective targeting of the PNS. BNB homing peptides will serve as selective discovery tools to unravel the biology of the barrier and will be amenable for further refinement in preclinical setting. Finally, we will examine BNB responses to perturbations like traumatic injuries or neuropathies and develop tools to specifically target the BNB.
Our project will transform the current understanding of the NV interface of the PNS, laying the foundation for targeted therapies to address BNB dysfunction and enhance clinical care for peripheral nerve disorders.
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Topic(s)

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HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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Call for proposal

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(opens in new window) ERC-2025-SyG

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Host institution

OSPEDALE SAN RAFFAELE SRL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 500 000,00
Address
VIA OLGETTINA 60
20132 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 500 000,00

Beneficiaries (4)

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