PRR7 as synaptic gatekeeper during neuroinflammation

• Applicants: Dr. Michael R. Kreutz; Professorin Dr. Marina Mikhaylova
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 523862973

Neuroinflammation has been linked to synapse loss and cognitive impairment, partly mediated by the proinflammatory cytokine IFN-y. Previous research suggests IFN-y impacts synaptic activity via regulation of AMPAR surface expression. In this project we will investigate the interaction between IFN-y signaling and the synaptic protein PRR7, elucidating its role in synaptic plasticity modulation during neuroinflammation. Preliminary findings reveal PRR7's role in regulating synaptic STAT1 levels, mitigating the negative effects of IFN-y on synaptic function. Here, we will focus on understanding how PRR7 might serve as synaptic gatekeeper in neuroinflammation, exploring potential therapeutic interventions such as AAV-based restoration of PRR7 levels, EV-mediated PRR7 delivery, and JAK signaling targeting to restore synaptic homeostasis. Through systematic exploration in three work packages, the project aims to provide insights into neuroinflammatory mechanisms and potential therapeutic avenues for cognitive dysfunction associated with increased IFN-y production.

• DFG Programme: Research Units
• Subproject of: FOR 5705: NeuroFlame – Defence and demise of inflamed neurons