Alexander Schaiter (Gießen / DE), Dr. Andreas Hentschel (Dortmund / DE), Prof. Dr. Andreas Hahn (Gießen / DE), Prof. Dr. Cornelia Kornblum (Bonn / DE), Prof. Dr. med Werner Stenzel (Berlin / DE), Dr. Alexander Mensch (Halle (Saale) / DE), Prof. Dr. Heidrun H. Krämer (Gießen / DE), PD Dr. Angela Rosenbohm (Ulm / DE), Prof. Dr. Marek Bartkuhn (Gießen / DE), PD Dr.rer nat Andreas Roos (Essen / DE), Prof. Dr. med Anne Schänzer (Gießen / DE)
Abstract-Text (inkl. Referenzen)
Pompe disease is a lysosomal storage disorder caused by mutations in the GAA gene encoding the enzyme α-1,4-glucosidase. GAA enzyme deficiency leads to reduced impaired muscle function and cell death. Although abnormal glycogen deposition and impaired autophagy contribute to muscle dysfunction, the precise pathomechanisms leading to cell death are still not clear. The aim of this study is to identify altered protein expression in Late Onset Pompe disease (LOPD) using proteomic analysis.
Skeletal muscle biopsies from 22 patients with LOPD prior to start of Enzyme replacement therapy (ERT) and from 11 age-matched controls were analysed using mass-spectrometry in an LFQ (label-free-quantification) experiment. Utilizing the GO and KEGG database an overrepresentation pathway analysis and a gene set enrichment analysis were conducted.
830 Proteins were identified of which 27 are up and 43 are down regulated. Most notably proteins associated with autophagy (e.g. LAMP2, RAB7A), mitotic cell cycle (e.g. NES), muscle function (e.g. TPM2, MYL5), and immune response (e.g. MIF, ANXA1) were dysregulated.
Mass-spectrometry analysis showed a significantly altered regulation in skeletal muscle samples from patients with Pompe disease compared to controls. Our findings collaborate the notion that muscle dysfunction and autophagy contribute to muscle pathology, whereas altered expression of immunoproteins suggest that immunological processes may also play a significant role in Pompe disease.