Skip to main content
Vai all'homepage della Commissione europea (si apre in una nuova finestra)
italiano it
CORDIS - Risultati della ricerca dell’UE
CORDIS

Deciphering the role of the blood-brain barrier in uremic toxins-induced neuropathies

Descrizione del progetto

Uno studio dell’impatto delle tossine uremiche sulla barriera emato-encefalica

La malattia renale cronica interessa oltre 840 milioni di persone in tutto il mondo e la sua prevalenza è in aumento a causa dell’invecchiamento e delle patologie correlate, con un conseguente aumento dei costi sanitari e dell’onere legato alla malattia. Negli stadi avanzati, la malattia renale cronica provoca l’accumulo di tossine nocive, note come tossine uremiche legate alle proteine (PBUT, Protein-Bound Uremic Toxins), che possono alterare la barriera emato-encefalica (BEE), con potenziali danni alla salute neurologica. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto BBB-UT si propone di sviluppare un dispositivo multi-organ-on-chip per svelare l’impatto delle PBUT sull’integrità e sulla funzionalità della BEE. Per farlo, concentrerà l’attenzione sulla disfunzione dell’asse rene-cervello nelle complicazioni neurologiche. Creando un modello di BEE on-chip basato sui microfluidi e collegato a un sistema rene on-chip, il progetto fornirà approfondimenti sull’integrità della BEE e sul comportamento delle PBUT, permettendo il progresso delle terapie per la malattia renale cronica.

Obiettivo

Chronic kidney disease (CKD) is estimated to affect more than 840 million people worldwide constituting a major global health crisis. Clinically, the number of CKD patients will continue to rise mostly because of the ageing population and the increased prevalence of comorbidities such as diabetes and hypertension. In Europe, around 100,000 million people are affected by it. According to the gloomy predictions, Europe is at risk of a dismal increase of CKD patients as well as costs to healthcare systems. Patients with advanced CKD display a loss of kidney function leading to a blood accumulation of, a.o. protein-bound uremic toxins (PBUTs) that are poorly eliminated by renal replacement therapies. This systemic retention known as the uremic syndrome affects other organs. Indeed, neurologic complications such as blood-brain barrier (BBB) disruption have been reported in CKD patients. The BBB guarantees the exchange between the blood and the brain through a complex cellular organization and a diverse range of transport proteins mediates the movement of endo/exogenous compounds.
I hypothesize that impairment of kidney tubular functionality in CKD causes an alteration of BBB integrity and function. This results in an aberrant BBB pass-through of PBUTs as well as impacts BBB vectorial transport capabilities. This fellowship aims to develop an appropriate multi-organs-on-chip device to accurately describe (i) the impact of PBUTs on BBB integrity and functionality, and (ii) the involvement of kidney-brain axis dysfunction in PBUTs-driven BBB disruption. We will develop a bioprinting-based microfluidic BBB-on-chip to accurately study BBB permeability, architecture, and transport function. This device will be connected to our established proximal tubule-on-chip to form a robust (kidney-brain) multi-organs-on-chip system. This project will pave the way toward the establishment of new and effective CKD therapies, and an expert system for pharmacology studies in a near future.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

Vedi tutti i progetti finanziati nell’ambito di questo schema di finanziamento

Invito a presentare proposte

(si apre in una nuova finestra) HORIZON-MSCA-2022-PF-01

Vedi tutti i progetti finanziati nell’ambito del bando

Coordinatore

UNIVERSITEIT UTRECHT
Contributo netto dell'UE
€ 187 624,32
Costo totale
Nessun dato