The following is a summary of “Schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking,” published in the September 2024 issue of Psychiatry by Phadke et al.
Neuroimmune interactions involving microglia and complement receptor 3 (CR3) play a crucial role in regulating synaptic plasticity in the brain, with pathological complement activity, such as C4 overexpression, linked to accelerated synaptic loss.
Researchers conducted a retrospective study to investigate C4-mediated cortical hypoconnectivity through the CR3 pathway or an alternative mechanism and to identify the intracellular processes involved in C4-OE.
They examined the role of C4-OE in synaptic loss by focusing on the trafficking of GluR1, a glutamate receptor subunit, and its relationship with the endosomal protein SNX27. C4-OE’s impact on synaptic connectivity in the prefrontal cortex and the potential for rescuing these alterations by increasing neuronal SNX27 levels were assessed.
The results showed that C4-mediated cortical hypoconnectivity is CR3-independent, while C4-OE triggered GluR1 trafficking through an intracellular mechanism with endosomal protein SNX27, causing synaptic loss.
They concluded complement activity linked to an intracellular endo-lysosomal trafficking pathway disrupting synaptic plasticity.
Source: nature.com/articles/s41380-024-02701-7
The post C4-OE Disrupts Synaptic Plasticity via SNX27 and Endosomal Pathways first appeared on Physician's Weekly.