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Proteasomal degradation of toxic intracellular amyloid-beta protein by nanobody-enabled proximity to ubiquitin ligase

Descripción del proyecto

Un tratamiento innovador para la enfermedad de Alzheimer

En la enfermedad de Alzheimer (EA), la producción de la proteína amiloide beta (Aβ) a partir de la proteína Aβ precursora supera su tasa de depuración, lo cual lleva a la acumulación anormal de la primera en placas amiloides. Estas formas tóxicas de Aβ provocan la neuroinflamación y la neurodegeneración, lo que conduce a la pérdida de funciones cognitivas en los pacientes con EA. El proyecto Protambbody, financiado con fondos europeos, propone guiar la eliminación del péptido Aβ mediante el sistema de degradación selectiva del proteasoma de la célula. Esta novedosa metodología presenta una prometedora estrategia de modificación de la enfermedad para la EA y ofrece una alternativa a las actuales e insatisfactorias iniciativas que promueven la inmunización contra el péptido Aβ.

Objetivo

The amyloid-beta (A) protein arises from the sequential proteolytic cleavage of A precursor protein (APP). The accumulation of A oligomers has been regarded as the causal factor of Alzheimers disease (AD). Basal metabolic production of the A peptide is typical in healthy people, and its production rate is normally lower than its rate of clearance. In AD, the uncontrolled accumulation of toxic forms of A stemming from problems in its clearance and degradation results in memory loss, chronic neuroinflammation and neurodegeneration. AD is a leading cause of disability and death both in Europe and the world, and currently has no cure or clinically-proven disease-modifying therapies.

There are over 10 million new cases of dementia each year worldwide (up to 80% of which are due to AD), implying one new case every 3.2 seconds. In Europe, about 10 million people currently suffer from this disease and about 50 million in the world; with these estimates projected to double by 2050. Thus, the identification of novel disease-modifying therapies has become very critical to eradicating AD from Europe and the world. My project proposes a radically novel approach in the AD field of utilizing the bodys cellular waste disposal system to selectively degrade A peptide, the causative agent of AD. This is in sharp contrast to the current approach of immunization against the A peptide, which has repeatedly failed to yield any cure or disease-modifying therapies for AD.

This project will aim to identify the specific cytotoxic A peptides responsible for neuroinflammation and neurodegeneration in human induced pluripotent stem cells and target these peptides for degradation by the ubiquitin proteasome system. Emphasis will be on the cytotoxic A peptides of intracellular origin as emerging targets in AD. This research will be conducted at the University of Helsinki, Finland, followed by a non-academic placement at Roche Diagnostics GmbH.

Ámbito científico (EuroSciVoc)

CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.

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Coordinador

HELSINGIN YLIOPISTO
Aportación neta de la UEn
€ 269 418,00
Dirección
FABIANINKATU 33
00014 HELSINGIN YLIOPISTO
Finlandia

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Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos

Socios (1)