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Lookup NU author(s): Professor Grainne Gorman, Professor Robert Taylor
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2024 The Royal Society of Chemistry.Neuromuscular disorders are a group of conditions that can result in weakness of skeletal muscles. Examples include fatal diseases such as amyotrophic lateral sclerosis and conditions associated with high morbidity such as myopathies (muscle diseases). Many of these disorders are known to have abnormal protein folding and protein aggregates. Thus, easy to apply methods for the detection of such changes may prove useful diagnostic biomarkers. Raman spectroscopy has shown early promise in the detection of muscle pathology in neuromuscular disorders and is well suited to characterising the conformational profiles relating to protein secondary structure. In this work, we assess if Raman spectroscopy can detect differences in protein structure in muscle in the setting of neuromuscular disease. We utilise in vivo Raman spectroscopy measurements from preclinical models of amyotrophic lateral sclerosis and the myopathy Duchenne muscular dystrophy, together with ex vivo measurements of human muscle samples from individuals with and without myopathy. Using quantitative conformation profiling and matrix factorisation we demonstrate that quantitative ‘conformational fingerprinting’ can be used to identify changes in protein folding in muscle. Notably, myopathic conditions in both preclinical models and human samples manifested a significant reduction in α-helix structures, with concomitant increases in β-sheet and, to a lesser extent, nonregular configurations. Spectral patterns derived through non-negative matrix factorisation were able to identify myopathy with a high accuracy (79% in mouse, 78% in human tissue). This work demonstrates the potential of conformational fingerprinting as an interpretable biomarker for neuromuscular disorders.
Author(s): Alix JJP, Plesia M, Dudgeon AP, Kendall CA, Hewamadduma C, Hadjivassiliou M, Gorman GS, Taylor RW, McDermott CJ, Shaw PJ, Mead RJ, Day JC
Publication type: Article
Publication status: Published
Journal: Analyst
Year: 2024
Volume: 149
Issue: 9
Pages: 2738-2746
Print publication date: 07/05/2024
Online publication date: 27/03/2024
Acceptance date: 11/03/2024
Date deposited: 14/05/2024
ISSN (print): 0003-2654
ISSN (electronic): 1364-5528
Publisher: Royal Society of Chemistry
URL: https://doi.org/10.1039/d4an00320a
DOI: 10.1039/d4an00320a
PubMed id: 38533726
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