An Optimized Comparative Proteomic Approach as a Tool in Neurodegenerative Disease Research

Abstract

Recent advances in proteomic technologies now allow unparalleled assessment of the molecular composition of a wide range of sample types. However, the application of such technologies and techniques should not be undertaken lightly. Here, we describe why the design of a proteomics experiment itself is only the first step in yielding high-quality, translatable results. Indeed, the effectiveness and/or impact of the majority of contemporary proteomics screens are hindered not by commonly considered technical limitations such as low proteome coverage but rather by insufficient analyses. Proteomic experimentation requires a careful methodological selection to account for variables from sample collection, through to database searches for peptide identification to standardised post-mass spectrometry options directed analysis workflow, which should be adjusted for each study, from determining when and how to filter proteomic data to choosing holistic versus trend-wise analyses for biologically relevant patterns. Finally, we highlight and discuss the difficulties inherent in the modelling and study of the majority of progressive neurodegenerative conditions. We provide evidence (in the context of neurodegenerative research) for the benefit of undertaking a comparative approach through the application of the above considerations in the alignment of publicly available pre-existing data sets to identify potential novel regulators of neuronal stability.

Aptamer-Based Proteomics Measuring Preoperative Cerebrospinal Fluid Protein Alterations Associated with Postoperative Delirium

“…Direct comparison of results across unique patient populations, applying different protein separation techniques and instrumentation for global protein analysis, is challenging to identify shared statistically significant protein changes [ 33 ]. However, additional cross-study confirmation can be derived from common altered biological pathways [ 34 ]. Poljak et al, 2014 [ 31 ] and Westoff et al, 2015 [ 32 ] both detected proteins altered in the acute-phase response, which is part of the inflammatory pathway, in agreement with our study’s identification of the inflammatory response.…”

Bringing synapses into focus: Recent advances in synaptic imaging and mass-spectrometry for studying synaptopathy

“…Thus, proteomics in neuroscience (“neuroproteomics”) is being increasingly implemented, due to the wide coverage capabilities and the functionally accurate data generated. Further, neuroproteomics can also be used to identify potential biomarkers or potential therapeutic targets within a pathological molecular process ( Hasin et al, 2017 ; Kline et al, 2022 ).…”