The Human Brain Proteome Project: Biological and Technological Challenges.

Brain proteomics has become a method of choice that allows zooming-in where neuropathophysiological alterations are taking place, detecting protein mediators that might eventually be measured in cerebrospinal fluid (CSF) as potential neuropathologically derived biomarkers. Following this hypothesis, mass spectrometry-based neuroproteomics has emerged as a powerful approach to profile neural proteomes derived from brain structures and CSF in order to map the extensive protein catalog of the human brain. This chapter provides a historical perspective on the Human Brain Proteome Project (HBPP), some recommendation to the experimental design in neuroproteomic projects, and a brief description of relevant technological and computational innovations that are emerging in the neurobiology field thanks to the proteomics community. Importantly, this chapter highlights recent discoveries from the biology- and disease-oriented branch of the HBPP (B/D-HBPP) focused on spatiotemporal proteomic characterizations of mouse models of neurodegenerative diseases, elucidation of proteostatic networks in different types of dementia, the characterization of unresolved clinical phenotypes, and the discovery of novel biomarker candidates in CSF.