Project description
An innovative treatment for Alzheimer’s disease
In Alzheimer’s disease (AD), production of the amyloid-beta (Aβ) protein from the Aβ precursor protein exceeds its clearance rate, leading to the aberrant accumulation of the former into amyloid plaques. These toxic forms of Aβ induce neuroinflammation and neurodegeneration, leading to the loss of cognitive functions in AD patients. The EU-funded Protambbody project proposes to guide Aβ peptide clearance by the selective proteosome degradation system of the cell. This novel approach presents a promising disease-modifying strategy for AD and offers an alternative to current, unsatisfactory efforts promoting immunisation against the Aβ peptide.
Objective
The amyloid-beta (Aβ) protein arises from the sequential proteolytic cleavage of Aβ precursor protein (APP). The accumulation of Aβ oligomers has been regarded as the causal factor of Alzheimer’s disease (AD). Basal metabolic production of the Aβ 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 Aβ 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 body’s cellular waste disposal system to selectively degrade Aβ peptide, the causative agent of AD. This is in sharp contrast to the current approach of immunization against the Aβ peptide, which has repeatedly failed to yield any cure or disease-modifying therapies for AD.
This project will aim to identify the specific cytotoxic Aβ 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 Aβ 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.
Fields of science
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- engineering and technologyenvironmental engineeringwaste management
- medical and health sciencesbasic medicineimmunologyimmunisation
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
00014 Helsingin Yliopisto
Finland