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.

Olfactory bulb proteome dynamics during the progression of sporadic Alzheimer's disease: identification of common and distinct olfactory targets across Alzheimer-related co-pathologies

“…Basically, the discovery strategy used was based on differential labeling of peptides using isobaric tags prior to their separation and analysis by multidimensional LC coupled to MS [ 45 ], revealing new insights into the OB site-specific proteomic signature during the progression of AD. More than 4,500 proteins have been identified in human OB, being one of the most extensive proteomic characterization of a human brain area [ 46 ]. 231 proteins were significantly altered between some AD phenotypes and neurologically intact controls, where 11 potential biomarkers identified in the OB region (Serum albumin, 14-3-3 protein epsilon, Isoform 3 of Inter-alpha-trypsin inhibitor heavy chain H4, Antithrombin-III, Hemopexin, C4b-binding protein alpha chain, Gamma enolase, Phosphatidylethanolamine binding protein 1, Glial fibrillary acidic protein, Neuronal pentraxin-1, and Neurofascin) (see Online Resource 5) have already been proposed for their potential usefulness in AD diagnosis [ 23 , 24 , 47 ].…”

Lipids and lipoxidation in human brain aging. Mitochondrial ATP-synthase as a key lipoxidation target

“…The human transcriptomics study demonstrates the existence of 20,344 putative protein-coding genes, with about 74% of these genes expressed in the brain compared to other human tissues [66]. More specifically, in total 10,465 protein entries (corresponding to 7797 protein-coding genes) have been detected and identified in healthy human brain by mass spectrometry-based proteomics [67]. Assuming this number of brain proteins, available evidence demonstrates that only 0.7% of the healthy adult brain proteome is lipoxidatively modified (71 proteins from 10,465) (see Table 2).…”

In Vivo Large Scale Mapping Of Protein Turnover In The Human Cerebrospinal Fluid

“…We used as reference plasma proteome the union of the plasma proteome database (Nanjappa et al, 2014) (PPD) and proteins annotated as plasma in UniProtKB/Swissprot. Similarly, we defined a reference CSF proteome by taking the union of CSF proteins reported in two comprehensive lists (Barkovits et al, 2018;Fernandez-Irigoyen et al, 2015). Potentially novel CSF proteins were (HUGO symbols for short) CEP290, FBXW10, KSR2, LOX, SH2D3A, SIK2, SPEN, TMEM212 and immunoglobulins (IGHV3-43, IGHV3-74, IGKV3D-15, IGKV4-1).…”