This project is funded under the UEFISCDI research plan, The Development of the national system of research and development and is part of the “HUMAN RESOURCES” Program: Postdoctoral research project (PD).
Contract no. 25/2018 PN-III-P1-1.1-PD-2016-0737
The role of physiologically relevant metal ions on amyloid-beta peptide oligomerization and neurotoxicity in condition resembling amyloidosis.
Alzheimer’s disease (AD) belongs to a class of degenerative diseases commonly referred to as a protein misfolding diseases, whose main pathological features are progressive depositions of Aß peptides plaques between nerve cells, and neurofibrillary tangles within the nerve cells. Neurotoxic amyloid peptides are initially released as a monomers, and fibril formation starts with the formation of soluble Aß oligomer species. These small oligomeric amyloids were shown to allow ion permeability through ion channels-like structures inserted into the cellular membrane, and have proven to produce amyloid toxicity. Although, there is evidence for Aß oligomers being a “toxic species” and it is also clear that metals ions enhances amyloid peptide misfolding, it is not clear whether there is a physiological role for metal-biding or whether metal-binding occurs only during Aß formation. Furthermore, knowing that the properties of the membranes influence biological functions, the question rises whether the interaction between metal and lipid membranes modulate in some manner the Aß insertion and activity. Considering the above, this project proposes the following: (1) the study of the activity of Aß peptide oligomers in reconstituted lipid membranes, in condition resembling amyloidosis and (2) elucidate through which interfacial interactions between electrophysiological relevant metals and reconstituted lipid membranes alter the membrane affinity and activity of selected ß-amyloids.