Descripción del proyecto
Determinación de la estructura de agregados de proteínas en la enfermedad de Alzheimer
La enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo progresivo que afecta sobre todo a la población de mayor edad. Se caracteriza por la acumulación de agregados de proteína τ y β amiloide en las neuronas. Se sabe que estos oligómeros proteicos son neurotóxicos, pero su estructura aún no se ha caracterizado en detalle. El objetivo del proyecto Oligomers-MAS-NMR, financiado con fondos europeos, es determinar la estructura y la interacción de los oligómeros β amiloide y τ con tecnologías punta. Los resultados del proyecto proporcionarán conocimientos fundamentales sobre el mal plegamiento de las proteínas y la agregación de proteínas en la EA, lo que posibilitará el diseño de nuevas estrategias de tratamiento.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Convocatoria de propuestas
Consulte otros proyectos de esta convocatoriaConvocatoria de subcontratación
H2020-WF-03-2020
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
LV-1006 Riga
Letonia