Introduction to the versatility of biomimetic membranes to characterize modulators of Aβ1-42 fibrillization with potential interest in Alzheimer's disease treatment

International audienceAlzheimer’s Alzheimer’s Alzheimer’s Alzheimer’s Alzheimer’s disease disease(AD) (AD) is the most widespread widespread widespread form of senile dementia dementia worldwide worldwide and representsrepresents represents the leading leading leading socioeconomic socioeconomic socioeconomicproblem problem in healthcare healthcare healthcarehealthcare .The onset onsetonsetand the progression progression progression of this thisneurodegenerative neurodegenerative disease disease is associated associated associated with with the aggregation aggregation of the amyloid amyloid -β peptide (Aβ) through afibrillization fibrillization process. Hence, an attractive attractive attractive attractive therapeutictherapeutic therapeutic strategy strategy against against this thisdisorderdisorder disorder is the development development developmentof molecules moleculesmolecules able able to interfere interfereinterfere interfere at specific specificsteps steps of thisthis fibrillization fibrillization fibrillization pathway pathway 1,i.e.able able to inhibit inhibit the formation of the soluble toxic toxicoligomeric oligomeric oligomericAβ aggregates. To identify identify such suchpromisingpromising therapeutic therapeutic therapeutic molecules, experimental experimental experimental experimentalexperimental methods methodsmethods are required in vitro vitro to precisely precisely follow and characterize characterize characterize thethe state state (monomer/oligomers (monomer/oligomers(monomer/oligomers /fibrils) /fibrils) /fibrils) and the conformation conformation conformation of Aβ peptide peptide duringduring its fibrillization fibrillization fibrillizationfibrillization process process .In the same time,time, these methods methods methodsmust mustbe simple enough to remain compatible compatiblecompatible compatible with the High High Throughput Throughput Screening Screening(HTS) of new compounds compounds with with potential potential interest interest in AD treatment treatment. In the present study, study, study,we propose propose to combine combine combineexperimental experimental experimental methods methodsto allow amultiparameter multiparameter multiparameter characterization characterization characterization characterization of potential potential modulators of Aβ 1-42 fibrillization fibrillization fibrillization. These Thesekinetickinetic kinetic studies studiesare carried carried out in presence presence of liposomes liposomes as biomimetic biomimetic biomimetic biomimeticneuronal neuronal neuronal membranes membranesmembranes membranes .Indeed, Indeed, it hashas been establishedestablished established established that lipidslipids lipids lipidsof thethe neuronal neuronalmembrane membrane are an important important factor factor in the cascade cascade of events that leads to the formation formation of the amyloid amyloid fibers