P04 - Interaction

PRR7 as synaptic gatekeeper during neuroinflammation

Neuroinflammation has been linked to synapse loss and cognitive impairment in various neurological disorders. One major mediator of this process is the proinflammatory cytokine interferon-gamma (IFN-γ), which disrupts synaptic activity partly through modulation of AMPA receptor (AMPAR) surface expression. However, the molecular mechanisms that protect synapses from IFN-γ-induced damage remain poorly understood. Our preliminary data suggest that PRR7 modulates synaptic STAT1 levels and may buffer the negative effects of IFN-γ on synaptic function. Despite this, the precise mechanisms by which PRR7 influences IFN-γ signalling at the synapse, and its potential as a therapeutic target, are yet to be elucidated. The central objective of our project is to determine whether PRR7 functions as a synaptic gatekeeper that maintains synaptic integrity during neuroinflammation.

In this project, we will employ a combination of cell biology, biochemistry and advanced microscopic imaging approaches organized into three work packages: (1) dissecting the molecular interaction between PRR7 and IFN-γ signaling pathways at the synapse, (2) testing AAV-based and extracellular vesicle (EV)-mediated strategies to restore PRR7 levels in inflammatory conditions, and (3) evaluating pharmacological interventions targeting JAK/STAT signaling to rescue synaptic plasticity. We aim to define a novel protective mechanism within synapses during neuroinflammation and identify potential therapeutic strategies for cognitive impairment linked to elevated IFN-γ levels. By characterizing PRR7’s function and testing targeted interventions, we hope to advance the understanding of synaptic adaptation to immune signaling and contribute to the development of new treatments for inflammation-related brain disorders.