Dataset Information

Integrated Computational Analysis Highlights unique miRNA Signatures in the Subventricular Zone and Striatum of GM2 Gangliosidosis Animal Models.

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.

SUBMITTER: Morena F

PROVIDER: S-EPMC6651736 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Integrated Computational Analysis Highlights unique miRNA Signatures in the Subventricular Zone and Striatum of GM2 Gangliosidosis Animal Models.

Morena Francesco F Oikonomou Vasileios V Argentati Chiara C Bazzucchi Martina M Emiliani Carla C Gritti Angela A Martino Sabata S

International journal of molecular sciences 20190628 13

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) ...[more]

PMID: 31261761

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Project description:ObjectiveLate-onset GM2 gangliosidosis (LOGG) subtypes late-onset Tay-Sachs (LOTS) and Sandhoff disease (LOSD) are ultra-rare neurodegenerative lysosomal storage disorders presenting with weakness, ataxia, and neuropsychiatric symptoms. Previous studies considered LOTS and LOSD clinically indistinguishable; recent studies have challenged this. We performed a scoping review to ascertain whether imaging and clinical features may differentiate these diseases.MethodsWe examined MEDLINE/non-MEDLINE databases up to May 2022. Articles reporting brain imaging findings in genetically/enzymatically confirmed LOGG, symptom onset at age ≥ 10 years (or evaluated at least once ≥18 years) were included, yielding 170 LOGG patients (LOTS = 127, LOSD = 43) across 68 papers. We compared LOTS versus LOSD and performed regression analyses. Results were corrected for multiple comparisons.ResultsAge of onset was lower in LOTS versus LOSD (17.9 ± 8.2 vs. 23.9 ± 14.4 years, p = 0.017), although disease duration was similar (p = 0.34). LOTS more commonly had psychosis/bipolar symptoms (35.0% vs. 9.30%, p = 0.011) but less frequent swallowing problems (4.10% vs. 18.60%, p = 0.041). Cerebellar atrophy was more common in LOTS (89.0%) versus LOSD (60.5%), p < 0.0001, with more severe atrophy in LOTS (p = 0.0005). Brainstem atrophy was documented only in LOTS (14.2%). Independent predictors of LOTS versus LOSD (odds ratio [95% confidence interval]) included the presence of psychosis/bipolar symptoms (4.95 [1.59-19.52], p = 0.011), no swallowing symptoms (0.16 [0.036-0.64], p = 0.011), and cerebellar atrophy (5.81 [2.10-17.08], p = 0.0009). Lower age of onset (0.96 [0.93-1.00], p = 0.075) and tremor (2.50 [0.94-7.43], p = 0.078) were marginally statistically significant but felt relevant to include in the model.InterpretationThese data suggest significant differences in symptomatology, disease course, and imaging findings between LOTS and LOSD.

Dataset Information

Integrated Computational Analysis Highlights unique miRNA Signatures in the Subventricular Zone and Striatum of GM2 Gangliosidosis Animal Models.

Publications

Integrated Computational Analysis Highlights unique miRNA Signatures in the Subventricular Zone and Striatum of GM2 Gangliosidosis Animal Models.

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