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The role of neuraminidase 1 on regulation of muscle mass and of proliferative cell potential

Grant number: 15/05215-0
Support Opportunities:Regular Research Grants
Duration: July 01, 2015 - June 30, 2018
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Edmar Zanoteli
Grantee:Edmar Zanoteli
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The neuraminidase-1 (Neu1) regulates the catabolism of sialoglycoconjugates in lysosomes. Congenital deficiency of Neu1 is the basis of sialidosis, severe neurosomatic disease associated with osteoskeletal deformities, hypotonia and weakness. Neu1 deficient mice develop an atypical form of muscle degeneration characterized by abnormal proliferation of fibroblasts, expansion of extracellular matrix (ECM), invasion of muscle fibers by fibroblasts cells, cytoplasm fragmentation, vacuolar formation and muscle atrophy. The occurrence of muscle atrophy indicates that the Neu1 must be related to the control of muscle mass, which is dependent on the balance between protein synthesis and degradation. Furthermore, we have recently demonstrated that the Neu1 deficiency affects the regenerative capacity of muscle tissue. The presence of excessive fibroblast proliferation suggests that Neu1 is also involved in the cellular proliferative potential control. Previous studies have shown that fibroblasts of patients with sialidosis show a high proliferative capacity possibly due to increased response to PDGF-BB and IGF-2. The objectives of this study are to investigate the expression of membrane receptors involved in cell proliferation pathways, such as IGFr and PDGFr, in skeletal muscle and in fibroblasts of Neu1 deficient mice, and evaluate the effects of receptors inhibiting drugs on ECM abnormalities in these animals. In addition, considering the importance of autophagy in the removal of proteins and organelles debris, this study aims to determine the effect of Neu1 deficiency on autophagy activation by food deprivation and administering drugs. Finally, considering that muscle atrophy is a major phenotypic change observed in animals with deficiency of Neu1, we aim to investigate whether cathepsins oversialilated act as one of the factors responsible for the development of muscle atrophy in these animals. The results obtained from this study will provide important information as to the involvement of Neu1 in the control of cell proliferation and control of muscle mass as well as the understanding of the pathogenesis of muscle phenotypic changes observed in Neu1 deficiency. (AU)

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