Hebah Fatafta

Hebah Fatafta

PGSB Fellow
Birzeit University & Heinrich Heine University Düsseldorf (HHU)

Department: Physics

Faculty: Faculty of Science

Specialization: Physics 

Accurate Specialization: Theortical physics

Palestinian supervisor:  Prof. Dr. Abdallah Sayyed-Ahmad

Degree aims: PhD

FZJ Supervisor: Prof. Dr. Birgit Strodel

Center in Juelich: Forschungszentrum Jülich (FZJ)

Affiliated University in Germany: Heinrich Heine University Düsseldorf (HHU)

Department: Chemistry

Faculty: Faculty of Mathematics and Natural Sciences

The mission research period : 07/2018 – 07/2021

Title of  Research: The simulation of amyloid aggregation under in vivo conditions

Research Purpose: The goal of this project is to simulate the aggregation of the amyloid-β peptide (Aβ), which is highly associated with the development of Alzheimer's disease (AD), in environments that consider certain aspects of the conditions found in the brain. This will be achieved by studying how the aggregation of Aβ is modified by neuronal lipid membranes, molecular crowding (i.e., the occurrence of high concentrations of other macromolecules), oxidative stress (i.e., the excess of reactive oxygen species), and combinations of these in vivo conditions using all atom molecular dynamics simulation (AA-MD).

Main outputs/results: Up to now, we found how different the different components of a neuronal lipid membrane affect the Aβ-membrane interactions. For example, we elucidated that electrostatic interactions between the peptide and lipids, such as POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine), and POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) are the driving force for the adsorption of Aβ to the membrane, while at the same time they inhibit Aβ to insert into the membrane, which would cause toxic membrane damage. For the presence of  a crowded environment we revealed that this condition has a considerable stabilizing effect on Aβ aggregation products.

Main Impact: Alzheimer’s disease (AD) is a neurodegenrative disorder known to be the 6th leading cause of death. All simulations studying Aβ aggregation published to date did not take into account the full complexity of the biological environment. Our research will help in filling the gap and facilitate an understanding of how the Aβ aggregation is modulated by mimicking the in vivo conditions. This might lay the ground for the development of new aggregation inhibitors for the therapy of AD that will help the society in overcoming the economic and social burdens of AD.

Publication:  Role of Oxidized Gly25, Gly29, and Gly33 Residues on the Interactions of Aβ1–42 with Lipid Membranes. H. Fatafta, C. Poojari, A. Sayyed-Ahmad, B. Strodel, M.C. Owen 2020, ACSChem. Neurosci. 2020, Vol. 11, pp. 535-548. DOI: 10.1021/acschemneuro.9b00558