Analysis of brain microRNAs in an animal model of mucopolysaccharidosis type I

• Grant number: 14/14230-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2015
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Vânia D'Almeida
• Grantee: Vanessa Gonçalves Pereira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Mucopolysaccharidosis type I (MPS I) is caused by deficiency of alpha-L-iduronidase (IDUA), which impairs the degradation of glycosaminoglycans in the lysosomes. Besides glycosaminoglycans accumulation, MPS I patients present high quantities of gangliosides in the brain, liver, spleen and kidneys. This secondary accumulation has also been observed in different brain structures from Idua knockout mice and is thought to contribute to the progression of neuropathology in the severe form of the disease. However, little is known about the mechanisms which lead to the accumulation of gangliosides in MPS I. A recent study demonstrated a reduction of Neu1 gene (involved in the degradation of gangliosides) expression in the brain of MPS I mice; therefore, it is possible that epigenetic mechanisms may be altered in these cells.The aim of this study is to evaluate the expression of miRNAs predicted to bind to Idua and Neu1 genes, in different brain structures from an animal model of MPS I, as a possible common mechanism regulating the degradation of glycosaminoglycans and gangliosides.The expression of Neu1 and the following miRNAs will be evaluated by real-time PCR: mmu-miR-17, mmu-miR-20a, mmu-miR-20b, mmu-miR-93, mmu-miR-106a and mmu-miR-106b. Both strands (5p and 3p) of each miRNA will be analyzed. ²-actin, snoRNA234 and U6snRNA will be used as endogenous controls. (AU)

Scientific publications

(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)

PEREIRA, VANESSA GONCALVES; QUEIROZ, MATHEUS TROVAO; D'ALMEIDA, VANIA. Differential expression of microRNAs from miR-17 family in the cerebellum of mucopolysaccharidosis type I mice. Gene, v. 595, n. 2, p. 207-211, DEC 31 2016. (15/05381-8, 14/14230-0)

DE QUEIROZ, MATHEUS TROVAO; PEREIRA, VANESSA GONCALVES; DO NASCIMENTO, CINTHIA CASTRO; D'ALMEIDA, VANIA. The Underexploited Role of Non-Coding RNAs in Lysosomal Storage Diseases. FRONTIERS IN ENDOCRINOLOGY, v. 7, SEP 21 2016. (14/14230-0)