Synapse-to-nucleus communication in Alzheimer’s disease

Understanding how fast events at synapses are converted into long-lasting changes of neuronal acti- vity is a very important question in neuroscience. Several recent studies demonstrated that synapses and nuclei are connected by bidirectional communication routes that enable the efficient transfer of information and regulate the long-term structural changes of neuronal function. Moreover, several studies suggest that the disturbance of these communication routes is a common principle in many neurodegenerative diseases. Our primary hypothesis is that alterations in synapse-to-nucleus transport represent a main event asso- ciated with synaptic dysfunction in Alzheimer’s disease, which can be exacerbated by dysmetabo- lism. In particular, STAD will evaluate the properties of three synapse-to-nucleus messengers (Jacob, RNF10 and ICD) by testing whether interfering with their nuclear import can be beneficial or detri- mental with respect to the progression of Alzheimer’s disease. This research question will be performed through the development of innovative experimental mo- dels, in which synaptic failure, amyloid load and dysmetabolism may reveal the complexity of the human pathology. Overall, STAD will provide a characterization of the role played by the different synapse-to-nucleus pathways in Alzheimer’s disease and will generate novel animal models linking Alzheimer’s disease and dysmetabolism, thus disclosing a picture of the complex interplay of path- ways underlying Alzheimer’s disease pathogenesis.