MODULATORY ROLE OF MONOMERIC AMYLOID BETA ON NEURONAL EXCITABILITY AND ITS IMPLICATIONS ON SYNAPTIC ACTIVITY OF IMMATURE CORTICAL NEURONS

So far the amyloid hypothesis has mainly driven the Alzheimer's Disease (AD) drugs development; however most of the anti Aβ-clinical trials have been suspended due to the lack of significant cognitive improvements as well as to the side effects caused in AD patients in some studies. Although the negative outcomes of β- and γ-secretases targeting therapies are reasonable explained by the significant biological functions covered by such proteases, the reason Aβ-centric therapies fail is still unclear. Thus, to design a successful therapy for AD it is therefore crucial to uncover the role of soluble endogenous Aβ in the healthy brain. Even though the amyloid peptide has been extensively studied because of its association to AD, its physiological function(s) is now being studied in much more detail. My thesis work is part of the recently emerging idea that Aβ – at low concentrations - is not just a toxic waste product of the brain but it might be a relevant element involved in the maintenance of neuronal network homeostasis. Our final goal is therefore to explore the effects of the monomeric Aβ1-42 peptide on excitable cells.