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Multi-Study Proteomic and Bioinformatic Identification of Molecular Overlap between Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA)

Bowerman; Fuller

Multi-Study Proteomic and Bioinformatic Identification of Molecular Overlap between Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA) Thumbnail


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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.

Acceptance Date Nov 30, 2018
Publication Date Dec 4, 2018
Publicly Available Date Mar 28, 2024
Journal Brain Sciences
Publisher MDPI
DOI https://doi.org/10.3390/brainsci8120212
Keywords spinal muscular atrophy; amyotrophic lateral sclerosis; proteomics; bioinformatics;
ER-Golgi trafficking; calreticulin; CALR; endoplasmic reticulum; calcium
Publisher URL https://doi.org/10.3390/brainsci8120212