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), invasion of muscle fibers by ECM components with cytosolic fragmentation, vacuolar formation and muscle atrophy. The aim of this study is to investigate the role of Neu1 on muscle atrophy and regeneration processes. Experimentally, the satellite cells proliferation, inflammatory response, muscle fiber maturation and fibrosis development during the muscle regeneration process induced by intramuscular administration of cardiotoxin will be assessed in Neu1 deficient mice. Neu1 deficient myoblasts will be assessed in vitro for proliferative, fusion and differentiation capacity. Muscle atrophy will be induced by sciatic nerve section in Neu1 deficient mice with the objective to assess the histological effects of Neu1 deficiency on skeletal muscle and autophagosome formation. In Neu1 deficient myoblasts submitted to food deprivation will be assessed for autophagosome formation. The determination of Neu1 role on muscle physiology will be of great value 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. (AU)
Articles published in Agência FAPESP Newsletter about the research grant:
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NEVES, JULIANA DE CARVALHO;
RIZZATO, VANESSA RODRIGUES;
GARCIA, MARIANA MIRANDA;
VAN DE VLEKKERT, DIANTHA;
Neuraminidase-1 mediates skeletal muscle regeneration.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,
Web of Science Citations: 4.
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