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DC Field | Value | Language |
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dc.contributor.author | Borg, Rebecca | - |
dc.contributor.author | Purkiss, Angie | - |
dc.contributor.author | Cacciottolo, Rebecca | - |
dc.contributor.author | Herrera, Paul | - |
dc.contributor.author | Cauchi, Ruben J. | - |
dc.date.accessioned | 2023-08-17T08:35:53Z | - |
dc.date.available | 2023-08-17T08:35:53Z | - |
dc.date.issued | 2023 | - |
dc.identifier.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. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/112358 | - |
dc.description.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. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier Inc. | en_GB |
dc.rights | info:eu-repo/semantics/restrictedAccess | en_GB |
dc.subject | Drosophila | en_GB |
dc.subject | Motor neurons | en_GB |
dc.subject | Neuromuscular diseases -- Case studies | en_GB |
dc.subject | Amyotrophic lateral sclerosis -- Diagnosis | en_GB |
dc.title | Loss of amyotrophic lateral sclerosis risk factor SCFD1 causes motor dysfunction in Drosophila | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1016/j.neurobiolaging.2023.02.005 | - |
dc.publication.title | Neurobiology of Aging | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
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Loss_of_amyotrophic_lateral_sclerosis_risk_factor_SCFD1_causes_motor_dysfunction_in_Drosophila.pdf Restricted Access | 2.5 MB | Adobe PDF | View/Open Request a copy |
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