title: Toward defining the anatomo-proteomic puzzle of the human brain: An integrative analysis.
abstract: The human brain is exceedingly complex, constituted by billions of neurons and trillions of synaptic connections that, in turn, define ∼900 neuroanatomical subdivisions in the adult brain (Hawrylycz et al. An anatomically comprehensive atlas of the human brain transcriptome. Nature 2012, 489, 391-399). The human brain transcriptome has revealed specific regional transcriptional signatures that are regulated in a spatiotemporal manner, increasing the complexity of the structural and molecular organization of this organ (Kang et al. Spatio-temporal transcriptome of the human brain. Nature 2011, 478, 483-489). During the last decade, neuroproteomics has emerged as a powerful approach to profile neural proteomes using shotgun-based MS, providing complementary information about protein content and function at a global level. Here, we revise recent proteome profiling studies performed in human brain, with special emphasis on proteome mapping of anatomical macrostructures, specific subcellular compartments, and cerebrospinal fluid. Moreover, we have performed an integrative functional analysis of the protein compilation derived from these large-scale human brain proteomic studies in order to obtain a comprehensive view of human brain biology. Finally, we also discuss the potential contribution of our meta-analysis to the Chromosome-centric Human Proteome Project initiative.
authors.affiliation: Clinical Neuroproteomics Group, Proteomics Unit, Proteored-ISCIII, Navarrabiomed, Fundación Miguel Servet, Pamplona, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Fernandez-Irigoyen
authors.affiliation: Bioinformatics Unit, Navarrabiomed, Fundación Miguel Servet, Pamplona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Labarga
authors.affiliation: Biofunctional Nanomaterials Laboratory, CIC Biomagune, San Sebastian, Spain.
authors.forename: Aintzane
authors.initials: A
authors.lastname: Zabaleta
authors.affiliation: Clinical Neuroproteomics Group, Proteomics Unit, Proteored-ISCIII, Navarrabiomed, Fundación Miguel Servet, Pamplona, Spain.
authors.forename: Xabier Martínez
authors.initials: XM
authors.lastname: de Morentin
authors.affiliation: Clinical Neuroproteomics Group, Proteomics Unit, Proteored-ISCIII, Navarrabiomed, Fundación Miguel Servet, Pamplona, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Perez-Valderrama
authors.affiliation: Neurological Tissue Bank, Navarrabiomed, Fundación Miguel Servet, Pamplona, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Zelaya
authors.affiliation: Clinical Neuroproteomics Group, Proteomics Unit, Proteored-ISCIII, Navarrabiomed, Fundación Miguel Servet, Pamplona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Santamaria
mesh_terms: D001921:Brain / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry; D040901:Proteomics / Q000379:methods*
keywords: Bioinformatics; Brain; Cerebrospinal fluid; Mass spectrometry; Proteomics