Progress toward a comprehensive brain protein interactome

Protein-protein interactions (PPIs) in the brain play critical roles across all aspects of the central nervous system, from synaptic transmission, glial development, myelination, to cell-to-cell communication, and more. Understanding these interactions is crucial for deciphering neurological mechanisms and the underlying biochemical machinery affected in neurological disorders. Recently, advances in proteomics techniques have significantly enhanced our ability to study interactions among the proteins expressed in the brain. Here, we review some of the high-throughput studies characterizing brain PPIs, using affinity purification, proximity labeling, co-fractionation, and chemical cross-linking mass spectrometry methods, as well as yeast two-hybrid assays. We present the current state of the field, discuss challenges, and highlight promising future directions.