Abstract
Mapping the intricate networks of cellular proteins in the human brain has the potential to address unsolved questions in molecular neuroscience, including the molecular basis of cognition, synaptic plasticity, long-term potentiation, learning, and memory. Perturbations to the protein-protein interaction networks (PPIN) present in neurons, glia, and other cell-types have been linked to multifactorial neurological disorders. Yet while knowledge of brain PPINs is steadily improving, the complexity and dynamic nature of the heterogeneous central nervous system in normal and disease contexts poses a formidable experimental challenge. In this review, the recent applications of functional proteomics and systems biology approaches to study PPINs central to normal neuronal function, during neurodevelopment, and in neurodegenerative disorders are summarized. How systematic PPIN analysis offers a unique mechanistic framework to explore intra- and inter-cellular functional modules governing neuronal activity and brain function is also discussed. Finally, future technological advancements needed to address outstanding questions facing neuroscience are outlined.