Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/112358
Title: Loss of amyotrophic lateral sclerosis risk factor SCFD1 causes motor dysfunction in Drosophila
Authors: Borg, Rebecca
Purkiss, Angie
Cacciottolo, Rebecca
Herrera, Paul
Cauchi, Ruben J.
Keywords: Drosophila
Motor neurons
Neuromuscular diseases -- Case studies
Amyotrophic lateral sclerosis -- Diagnosis
Issue Date: 2023
Publisher: Elsevier Inc.
Citation: Borg, R., Purkiss, A., Cacciottolo, R., Herrera, P., & Cauchi, R. J. (2023). Loss of amyotrophic lateral sclerosis risk factor SCFD1 causes motor dysfunction in Drosophila. Neurobiology of Aging, 126, 67-76.
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease mostly resulting from a complex interplay between genetic, environmental and lifestyle factors. Common genetic variants in the Sec1 Family Domain Containing 1 (SCFD1) gene have been associated with increased ALS risk in the most extensive genome-wide association study (GWAS). SCFD1 was also identified as a top-most significant expression Quantitative Trait Locus (eQTL) for ALS. Whether loss of SCFD1 function directly contributes to motor system dysfunction remains unresolved. Here we show that moderate gene silencing of Slh, the Drosophila orthologue of SCFD1, is sufficient to cause climbing and flight defects in adult flies. A more severe knockdown induced a significant reduction in larval mobility and profound neuromuscular junction (NMJ) deficits prior to death before metamorphosis. RNA-seq revealed downregulation of genes encoding chaperones that mediate protein folding downstream of Slh ablation. Our findings support the notion that loss of SCFD1 function is a meaningful contributor to ALS and disease predisposition may result from erosion of the mechanisms protecting against misfolding and protein aggregation.
URI: https://www.um.edu.mt/library/oar/handle/123456789/112358
Appears in Collections:Scholarly Works - FacM&SPB

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