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Proteomes Journal Special Issue "Neuroproteomics"

Recent advances in mass spectrometry (MS) instrumentation that enable the level of quantitation of expression of about 8000 proteins to be interrogated by LC/MS/MS analysis have opened the door to the proteome and already are having an impact that extends from biology to clinical proteomics. With no theoretical limits in sight with regard to further improvements in MS instrumentation and when coupled with new chemical labeling technologies that incorporate multiple isobaric tags that enable the concurrent analyses of up to 11 different samples using commercially available reagents, and improved peptide identification algorithms and bioinformatics; the future of MS-based, quantitative proteomics is incredibly promising and exciting for mass spectrometrists and for the much larger numbers of investigators whose research now depends upon MS/proteomics analyses. While these methods are beginning to be applied to neuroproteomics, the central nervous system (CNS) poses many challenges to quantitative proteomics that begin with the immense level of cellular and sub-cellular heterogeneity. The CNS has approximately 100 billion neurons, each with 10,000 to 100,000 synaptic connections; and even larger numbers of glial cells. Moreover, there is a large variety in cell morphology with individual neurons typically being intermingled in close contact with several different types of neurons and with axonal projections from an individual neuron often projecting over relatively long distances. Given that it is now clear that each of the approximately 1000 individual types of nerve cells exhibit distinct patterns of gene expression, it is critically important to develop and publish the technologies and methodologies needed to enable quantitative MS/proteomic analyses of specific neuronal cell types and their organelles.
While the whole brain or large regions of brain tissue can be used for proteomic analysis, the useful information that can be gathered is limited because of cellular and sub-cellular heterogeneity. Analysis of mixed populations of distinct cell types not only limits our understanding of where a particular protein expression change might have occurred, it also minimizes our ability to detect significant changes in protein expression and/or modification levels due to issues related to low signal to high noise.

As described in more detail in the accompanying Editorial, the articles in the Neuroproteomics Special Issue, which soon will be published as a book, provide an overview of the unique challenges that must be addressed to carry out meaningful MS/proteomics analyses on neural tissues and the tools and technologies that are available to meet these challenges. The several articles that cover drug addiction, as well as Alzheimer’s Disease, and schizophrenia illustrate how MS/proteomics technologies can be used to help improve our ability to diagnose and understand the molecular basis for neurological diseases. We believe that several of the articles in this Special Issue also will be of interest to investigators beyond the field of neurological disorders. In particular, the review by Carlyle et al (2018), “Proteomic Approaches for the Discovery of Biofluid Biomarkers of Neurodegenerative Dementias”, may be of interest to investigators searching for blood and CSF biomarkers for virtually any disease. Similarly, the review by Natividad et al (2018), “From Synapse to Function, A Perspective on the Role of Neuroproteomics in Elucidating Mechanisms of Drug Addiction”, provides a general overview of the utility of MS/proteomics approaches for addressing critical questions in addiction neuroscience that should be equally applicable to investigators involved in virtually any area of biomedical research. Likewise, the article by Wilson et al (2019), “Development of Targeted Mass Spectrometry-Based Approaches for Quantitation of Proteins Enriched in the Postsynaptic Density”, may be useful for any investigator who wishes to design and validate DIA and/or PRM assays for virtually any proteins. Finally, the peroxidase-mediated proximity labeling technology described in the article by Cijsouw et al (2018), “Mapping the Proteome of the Synaptic Cleft through Proximity Labeling Reveals New Cleft Proteins”, may be of interest to investigators interested in mapping many other spatially restricted proteomes.