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.