Abstract
Protein–protein interaction networks and signaling complexes are essential for normal brain function and are often dysregulated in neurological disorders. Nevertheless, unraveling neuron- and synapse-specific proteins interaction networks has remained a technical challenge. New techniques, however, have allowed for high-resolution and high-throughput analyses, enabling quantification and characterization of various neuronal protein populations. Over the last decade, mass spectrometry (MS) has surfaced as the primary method for analyzing multiple protein samples in tandem, allowing for the precise quantification of proteomic data. Moreover, the development of sophisticated protein-labeling techniques has given MS a high temporal and spatial resolution, facilitating the analysis of various neuronal substructures, cell types, and subcellular compartments. Recent studies have leveraged these novel techniques to reveal the proteomic underpinnings of well-characterized neuronal processes, such as axon guidance, long-term potentiation, and homeostatic plasticity. Translational MS studies have facilitated a better understanding of complex neurological disorders, such as Alzheimer’s disease (AD), Schizophrenia (SCZ), and Autism Spectrum Disorder (ASD). Proteomic investigation of these diseases has not only given researchers new insight into disease mechanisms but has also been used to validate disease models and identify new targets for research.
Highlights
Elaborate and tightly regulated protein–protein interaction (PPI) networks underlie key neuronal processes like axon guidance and synaptic plasticity, which are essential for the initial wiring and ongoing plasticity of the brain
Continuing advances made in areas from cell-specific purification, protein labeling, enrichment of peptides with post-translational modifications (PTMs), mass spectrometry (MS) instrumentation, data interpretation and bioinformatic analysis have elevated MS-based proteomics analysis from a general tool to a precision instrument with new relevance to research in both basic neuroscience and neurological disease
This study focused on adult tissue, application of cell type-specific Bio-orthogonal non-canonical amino acid tagging (BONCAT) in younger animals may shed a light on how different cells in the nervous system initially develop and wire up with their neighbors
Summary
Elaborate and tightly regulated protein–protein interaction (PPI) networks underlie key neuronal processes like axon guidance and synaptic plasticity, which are essential for the initial wiring and ongoing plasticity of the brain. Continuing advances made in areas from cell-specific purification, protein labeling, enrichment of peptides with PTM, MS instrumentation, data interpretation and bioinformatic analysis have elevated MS-based proteomics analysis from a general tool to a precision instrument with new relevance to research in both basic neuroscience and neurological disease. Researchers can see beyond cellular proteomes and zeroin on specific subcellular locales using proximity labeling assays, like APEX, BioID, and TurboID (Roux et al, 2013; Lobingier et al, 2017; Branon et al, 2018; Figure 3B) These approaches involve targeting an enzyme to an area of interest where it can modify a freely diffusing molecule–usually biotin– which, once modified, can attach itself to nearby proteins, allowing their later purification. Expansion of proteomic techniques in disease research will be important to furthering our understanding of AD and other diseases
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