Synapse-to-nucleus communication in Alzheimer's disease
In neurodegenerative diseases, specific events lead to progressive defects of neuronal function culminating in neuronal death. Growing evidence demonstrate that synaptonuclear protein messengers play key roles in synaptic function and plasticity and suggest that disturbance of intracellular transport processes is a common principle in many neurodegenerative diseases. However, at present no information are available about the role of specific synapse-to-nucleus transport in neurodegenerative diseases, i.e. Alzheimer Disease (AD). Based on the consideration that different synaptic versus extra-synaptic signals induce the nuclear import of specific protein messengers, here we will evaluate their properties 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 synaptonuclear messengers (Jacob, RNF10, PS1-ICD) addressing their role in the regulation of gene expression in AD and PD and on glutamatergic synapses in two brain regions the hippocampus and striatum, where synaptic dysfunction has been already described to occur in the early stages of these diseases. This approach will allow to characterize and compare different synaptonuclear messengers in AD models and to understand their role in inducing alteration of synaptic function and plasticity. To reach this goal we will use a vast array of experimental approaches available within the consortium, ranging from molecular biology and time-lapse confocal imaging to electrophysiology, optogenetics, and newly generated in vivo reporter systems.
- Principal Investigators:
- Financing institution:
- MINISTERO DELL'ISTRUZIONE E DEL MERITO
- JPI_MIUR - Joint Programming Initiatives_MIUR
- Project leader:
- UNIVERSITA' DEGLI STUDI DI MILANO