Description:

Multilevel Proteomic Investigations of Dendritic Spine Loss in Schizophrenia

The loss of dendritic spines, the postsynaptic component of excitatory synapses, is believed to underlie multiple symptom domains in schizophrenia, such as impairments in working memory and sensory processing. Dovetailing with these finding, unbiased genetic and pharmacologic studies consistently implicate postsynaptic protein networks. However, the mechanism by which genetic risk converges on postsynaptic protein networks, impairing synaptic function is unknown. Dendritic spines are regulated my multiple features of synaptic protein network such as protein trafficking, expression, and posttranslational modifications. We utilize mass spectrometry-based proteomics to investigate these various features in human postmortem brain tissue to identify candidate drivers of dendritic spine loss in disease.