Soltic, D, Bowerman, M ORCID: 0000-0002-3579-6403, Stock, J, Shorrock, HK, Gillingwater, TH and Fuller, HR ORCID: 0000-0001-8868-896X (2018) Multi-Study Proteomic and Bioinformatic Identification of Molecular Overlap between ALS and SMA. Brain Sciences. ISSN 2076-3425 (In Press)

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Abstract

Unravelling the complex molecular pathways responsible for motor neuron degeneration in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) remains a persistent challenge. Interest is growing in the potential molecular similarities between these two diseases, with the hope of better understanding disease pathology for the guidance of therapeutic development. The aim of this study was to conduct a comparative analysis of published proteomic studies of ALS and SMA, seeking commonly dysregulated molecules to be prioritised as future therapeutic targets. Fifteen proteins were found to be differentially expressed in two or more proteomic studies of both ALS and SMA, and bioinformatics analysis identified over-representation of proteins known to associate in vesicles, and molecular pathways, including metabolism of proteins and vesicle-mediated transport; both of which converge on ER-Golgi trafficking processes. Calreticulin, a calcium-binding chaperone found in the ER, was associated with both pathways and we independently confirm that its expression was decreased in spinal cords from SMA and increased in spinal cords from ALS mice. Together, these findings offer significant insights into potential common targets that may help to guide the development of new therapies for both diseases.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via MDPI at https://www.mdpi.com/journal/brainsci. Please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: spinal muscular atrophy; amyotrophic lateral sclerosis; proteomics; bioinformatics; ER-Golgi trafficking; calreticulin; CALR; endoplasmic reticulum; calcium
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Depositing User: Symplectic
Date Deposited: 03 Dec 2018 11:11
Last Modified: 03 Dec 2018 11:11
URI: http://eprints.keele.ac.uk/id/eprint/5535

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