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Impact of Lipid Cell Composition on Beta-Amyloid Aggregation: Exploring Novel Therapeutic Targets for Alzheimer's Disease

Project description

Cell membrane lipids and Alzheimer’s disease

Amyloid beta (Aβ) peptides are endogenously produced in the brain following cleavage of the amyloid precursor protein. Under normal conditions, these peptides serve certain physiological roles. However, their propensity to aggregate and accumulate is a central feature of Alzheimer’s disease pathology and leads to neurodegeneration and progressive cognitive decline. Emerging evidence underscores a role of various cellular factors in Aβ aggregate formation including cell membrane lipids. The scope of the EU-funded ABlina project is to precisely gauge the impact of membrane lipids on Aβ aggregation. The identification of specific lipids that promote or prevent aggregation is expected to open new avenues for therapeutic interventions in Alzheimer’s disease.

Objective

The ABlina project aims to study how cell membrane lipid composition affects the formation and deposition of beta amyloid (Aβ) aggregates. To achieve this, Molecular Dynamics (MD) simulations will be performed on membranes with varying lipid compositions, focusing on models that mimic senescent and Alzheimer's disease cells. The data generated will contribute to the establishment of a database, which will be subsequently analysed, to identify lipid patterns capable of modulating the behaviour of Aβ aggregation. If lipids promoting aggregation are identified, novel drugs could be formulated to inhibit their synthesis or interaction with Aβs, thereby preventing aggregation. Conversely, if any lipid is found to avoid aggregation, strategies could be designed to augment its presence within cerebral cells. To address the inherent spatial and temporal limitations of Molecular Dynamics (MD), Coarse-Grained (CG) modelling will be utilized. The project will be conducted at ITQB NOVA (University NOVA of Lisbon), under the supervision of Dr. Manuel N. Melo, a key contributor to the development of the original Martini Force Field, a widely recognized CG model that will be employed in this study. Through Dr. Melo's mentorship, I will receive advanced training in CG model development, enabling the accurate parameterization of lipids relevant to the project and enhancing the robustness of the database. The combination of Dr. Melo's extensive proficiency in CG methodologies and my prior experience in MD simulations and database management will establish a synergistic collaboration, expanding both my expertise and that of the host research group.
Overall, my project employs an innovative approach to investigate the relationship between cell membrane composition and Aβ aggregation, potentially revealing lipid membrane composition as a promising therapeutic target against Alzheimer’s disease.

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Topic(s)

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

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Call for proposal

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(opens in new window) HORIZON-WIDERA-2024-TALENTS-02

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Coordinator

UNIVERSIDADE NOVA DE LISBOA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 191 343,12
Address
CAMPUS DE CAMPOLIDE
1099 085 Lisboa
Portugal

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Activity type
Higher or Secondary Education Establishments
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Total cost

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