Descrizione del progetto
Determinare la struttura degli aggregati proteici nella malattia di Alzheimer
La malattia di Alzheimer è un disturbo neurodegenerativo progressivo che colpisce soprattutto la popolazione anziana, caratterizzato dall’accumulo di aggregati di beta-amiloide e proteina tau nelle cellule neuronali. Questi oligomeri proteici, fermo restando la loro accertata neurotossicità, non sono mai stati strutturalmente caratterizzati nel dettaglio. Il campo di applicazione del progetto Oligomers-MAS-NMR, finanziato dall’UE, è determinare la struttura e l’interazione degli oligomeri di beta amiloide e tau avvalendosi di tecnologie all’avanguardia. I risultati del progetto forniranno conoscenze fondamentali in merito all’errato ripiegamento proteico e all’aggregazione nella malattia di Alzheimer, aprendo nuove possibilità per la progettazione di strategie di trattamento innovative.
Obiettivo
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder responsible for about 2 million deaths per year. Despite tremendous progress in basic research within the last years, its efficient treatment and diagnostic tools are still lacking. The previous studies have gathered sufficient evidence of a causative role of the aggregates of two proteins - amyloid beta and tau - in the AD pathogenesis. Both of these proteins can form highly toxic oligomeric species, which are the primary suspects of AD-related neurotoxicity. However, due to experimental difficulties the detailed structural and functional characterization of the oligomeric forms has been a big challenge. In the proposed project we aim to build on cutting-edge technologies and novel approaches to obtain atomic-level structures and investigate interactions of the amyloid beta and tau oligomers. Thus, this multidisciplinary project will apply (I) cell-free protein expression and purification protocols for incorporation of various selectively 13C, 15N and 19F labeled amino-acids; (II) microfluidics in order to generate size-controlled oligomers (III) solid-state NMR (ssNMR) at fast magic-angle spinning (MAS) regime tailored for 1H and 19F detection schemes. The anticipated outcome of this will be a unique combination of approaches to study amyloid aggregates, which can be further used and adapted for studying other protein assemblies. The project results will form the basis of innovation in the treatment of AD as well as other tauopathies.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
LV-1006 Riga
Lettonia