Integrated computational analysis highlights unique miRNA signatures in the subventricular zone and striatum of GM2 gangliosidosis animal models

Francesco Morena, Vasileios Oikonomou, Chiara Argentati, Martina Bazzucchi, Carla Emiliani, Angela Gritti, Sabata Martino

Research output: Contribution to journalArticlepeer-review

Abstract

This work explores for the first time the potential contribution of microRNAs (miRNAs) to the pathophysiology of the GM2 gangliosidosis, a group of Lysosomal Storage Diseases. In spite of the genetic origin of GM2 gangliosidosis, the cascade of events leading from the gene/protein defects to the cell dysfunction and death is not fully elucidated. At present, there is no cure for patients. Taking advantage of the animal models of two forms of GM2 gangliosidosis, Tay-Sachs (TSD) and Sandhoff (SD) diseases, we performed a microRNA screening in the brain subventricular zone (SVZ) and striatum (STR), which feature the neurogenesis and neurodegeneration states, respectively, in adult mutant mice. We found abnormal expression of a panel of miRNAs involved in lipid metabolism, CNS development and homeostasis, and neuropathological processes, highlighting region- and disease-specific profiles of miRNA expression. Moreover, by using a computational analysis approach, we identified a unique disease- (SD or TSD) and brain region-specific (SVZ vs. STR) miRNAs signatures of predicted networks potentially related to the pathogenesis of the diseases. These results may contribute to the understanding of GM2 gangliosidosis pathophysiology, with the aim of developing effective treatments.

Original languageEnglish
Article number3179
JournalInternational Journal of Molecular Sciences
Volume20
Issue number13
DOIs
Publication statusPublished - Jul 1 2019

Keywords

  • Epigenetics
  • Hexosaminidase
  • Lysosomal storage disorders
  • Striatum
  • Subventricular zone

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Integrated computational analysis highlights unique miRNA signatures in the subventricular zone and striatum of GM2 gangliosidosis animal models'. Together they form a unique fingerprint.

Cite this