Mucopolysaccharidosis type I (MPS I) is a genetic disorder in which there is a deficiency in alpha-L-iduronidase (IDUA gene) enzyme expression, responsible for the lysosomal degradation of two glycosaminoglycans. Lysosomal disturbance caused by glycosaminoglycans accumulation triggers secondary effects among which gangliosides GM2, GM3 and GD3 storage on central nervous system (CNS), involved on neurodegenerative process observed in MPS I. Recent studies have showed the expression of genes responsible for gangliosides metabolism are found to be significantly reduced on MPS I mice cerebellum and hippocampus, especially Neu1 gene which encodes neuraminidase 1 enzyme. Together, neuraminidase 1, cathepsin A (Ctsa gene) and beta-galactosidase (Glb1 gene) enzymes belong to the lysosomal multienzyme complex (LMC), associated to some important functions like neuronal apoptosis. A preliminary study done by our group has showed that besides the reduction of Neu1 expression, there are alterations on three miRNAs levels from family miR-17 on MPS I mice, which only miR-20b-5p presents as predicted targets both Ctsa and Neu1 genes. Overexpression of miR-20b-5p and underexpression of miR-20b-3p on MPS I mice cerebellum are evidences of the importance of this pair in CNS physiopathology. Functional characterization of these miRNAs is an important step toward elucidation of the relationship between LMC and gangliosides storage. Therefore, our objective is to evaluate in vitro if neuraminidase 1 is regulated directly by miR-20b-5p and analyze the observed effects on gene and protein expression of LMC members in a high miR-20b-5p level context.
News published in Agência FAPESP Newsletter about the scholarship: