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Synapse-to-nucleus communication in Alzheimer’s disease


Start Date
End Date
Total Funding
€ 838 087
Funding Programme
European Countries Involved
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.
Project partners
University of Milano
Université de Bordeaux
Leibniz Institute for Neurobiology
Alzheimer Europe's database on research projects was developed as part of the 2020 Work Plan which received funding under an operating grant from the European Union’s Health Programme (2014–2020).