Dysregulation of metabolism and proteostasis in skeletal muscle of a presymptomatic Pompe mouse model

  • Pompe disease is a rare genetic metabolic disorder caused by mutations in acid-alpha glucoside (GAA) leading to pathological lysosomal glycogen accumulation associated with skeletal muscle weakness, respiratory difficulties and cardiomyopathy, dependent from the GAA residual enzyme activity. This study aimed to investigate early proteomic changes in a mouse model of Pompe disease and identify potential therapeutic pathways using proteomic analysis of skeletal muscles from pre-symptomatic Pompe mice. For this purpose, quadriceps samples of \(Gaa^{6neo/6neo}\) mutant (Pompe) and wildtype mice, at the age of six weeks, were studied with three biological replicates for each group. The data were validated with skeletal muscle morphology, immunofluorescence studies and western blot analysis. Proteomic profiling identified 538 significantly upregulated and 16 significantly downregulated proteins in quadriceps muscles derived from Pompe animals compared to wildtype mice. The majority of significantly upregulated proteins were involved in metabolism, translation, folding, degrading and vesicular transport, with some having crucial roles in the etiopathology of other neurological or neuromuscular diseases. This study highlights the importance of the early diagnosis and treatment of Pompe disease and suggests potential add-on therapeutic strategies targeting protein dysregulations.

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Author:Marlena RohmORCiDGND, Leon VolkeORCiDGND, Lara SchlaffkeORCiDGND, Robert RehmannORCiDGND, Nicolina Nathalie SüdkampGND, Andreas RoosORCiDGND, Anne SchänzerGND, Andreas HentschelORCiDGND, Matthias VorgerdORCiDGND
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2024/01/30
Date of first Publication:2023/06/11
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
Pompe disease; \(Gaa^{6neo/6neo}\) mouse; muscular disease; proteomics
Issue:12, Article 1602
First Page:1602-1
Last Page:1602-15
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Neurologische Universitätsklinik und Poliklinik
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International