P5.66 The role of Neuraminidase 1 on skeletal muscle regeneration

Abstract

Neuraminidase-1 (Neu1) regulates the catabolism of sialoglycoconjugates in lysosomes. Congenital Neu1 deficiency in children is the basis of sialidosis, a neurosomatic disorder whose symptoms include hypotonia, muscle weakness and osteoskeletal deformities. Mice with Neu1 deficiency develop an atypical form of muscle degeneration characterized by abnormal fibroblast proliferation and expanded extra cellular matrix (ECM), with invasion of muscle fibers by ECM components, cytosolic fragmentation, vacuolar formation and muscle atrophy. The aim of this study is to investigate the role of Neu1 on muscle regeneration process. Experimentally, inflammatory response, muscle fiber maturation and fibrosis development during the muscle regeneration process induced by intramuscular administration of cardiotoxin were assessed in Neu1 deficient mice. Muscle fiber maturation was not affected in Neu1 mice during regeneration. However, there were an accumulation of inflammatory cells and increase of ECM components that might affect the normal muscle tissue morphology during the muscle regeneration process. The determination of Neu1 role on muscle physiology is important to understand the neuromuscular clinical manifestations reported in patients with Neu1 deficiency and the importance of lysosomes and the sialic acid metabolism on the physiopathogenesis of muscle diseases (sponsored by FAPESP no 2009/02937-4).