Project: Synapse-to-nucleus communication in Alzheimer's disease

Acronym	STAD (Reference Number: 94)
Duration	01/06/2016 - 31/05/2019
Project Topic	Recent evidence demonstrates that protein transport from synapse-to-nucleus plays key roles in synaptic function and plasticity. Moreover, several studies suggest that disturbance of intracellular transport processes is a common principle in many neurodegenerative diseases. STAD primary hypothesis is that alterations in synapse-to-nucleus transport represent a main pathway leading to synaptic dysfunction in Alzheimer's disease (AD), which can be exacerbated by dysmetabolism. Different synaptic versus extra-synaptic signals induce the nuclear import of specific protein messengers. Here we will evaluate the properties of these messengers by testing whether interfering with their nuclear import can be beneficial or detrimental with respect to progression of neurodegenerative diseases. In particular, we will focus on recently described synapto-nuclear messengers (Jacob, RNF10, ICD) addressing their role in the regulation of gene expression in AD and on glutamatergic synapses in a brain region, the hippocampus, where synaptic dysfunction has been described to occur in the early stages of the disease. This research question will be attained through the development and use of innovative experimental models, in which synaptic failure, amyloid load and dysmetabolism may reveal the complexity of pathways involved in the human pathology. Moreover, we will use a vast array of approaches available within the consortium, ranging from molecular biology and time-lapse confocal imaging to electrophysiology, optogenetics, and newly generated in vivo reporter systems. The implementation of STAD will provide a full characterization of the specific role played by the different synapse-to-nucleus pathways in AD pathogenesis and will generate novel animal models linking AD and MetS, thus disclosing a complete picture of the complex interplay of pathways underlying AD pathogenesis.
Network	JPco-fuND
Call	Neurodegenerative diseases: risk and protective factors, longitudinal cohort approaches and advanced experimental models

Project partner

Number	Name	Role	Country
1	Università degli Studi di Milano	Coordinator	Italy
2	Centre National de la Recherche Scientifique	Partner	France
3	Leibniz Institute for Neurobiology	Partner	Germany