Title

 

Authors

C. Lanni, E. Mura

Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia

 

Abstract

Beta-amyloid (Ab) is considered one of the main pathogenetic factors of Alzheimer’s Disease (AD). Although the direct and indirect neurotoxic activity of Abare unchallenged, recent findings suggest that the peptide may have different biological roles. The idea is that Aβ may be important in normal brain functioning, regulating signalling between cells and signal transduction within a cell. When exceeding certain concentrations, as it happens during the disease, the peptide may lose these regulatory activities and become neurotoxic. Indeed the peptide exerts synaptic activities altering the control of the release of various neurotransmitters through actions played both at presynaptic receptors and on transduction pathways. Low amounts of soluble Ab, not only may disrupt synaptic terminal function at molecular level, but also deregulate pathways involved in cell cycle control and repair after cell damage and thus may contribute to AD pathogenesis leading to dysfunctional neurons. Whether the above mentioned effects are exerted on all the neurons, on the entire neuron, or separately at neuronal soma and terminals of different neuronal populations has to be established as well as the threshold concentrations responsible for each of these actions before toxicity happens. These roles of the peptide should be further explored since they may be at borderline between physiology and pathology. A more detailed characterization of the isoforms of the peptide responsible for these effects, of the time scale and of the involved cellular targets is important to better understand the prodromic stages of the disease and to develop more specific therapeutic strategies.