Gangliosides in nervous system development, regeneration, and pathologies

Vasques, Juliana Ferreira; Gonçalves, Renata Guedes de Jesus; Silva-Júnior, Almir Jordão da; Martins, Robertta Silva; Gubert, Fernanda; Mendez-Otero, Rosália

doi:10.4103/1673-5374.343890

Cited by 15 publications

(5 citation statements)

References 109 publications

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“…Common subclasses of sphingolipids include ceramides, sphingomyelins, glycosphingolipids (including cerebrosides and gangliosides) and sphingosine-1-phosphate. Each subclass has distinct structural features and biological functions that contribute to the overall diversity and complexity of sphingolipid metabolism and signalling in cells [ 28 , 29 , 30 , 31 ]. Glicerophospholipids in lipid rafts often have saturated acyl chains.…”

Section: Structure and Function Of Lipid Raftsmentioning

confidence: 99%

Lipid Rafts: The Maestros of Normal Brain Development

Viljetić,

Blažetić,

Labak

et al. 2024

Biomolecules

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Lipid rafts, specialised microdomains within cell membranes, play a central role in orchestrating various aspects of neurodevelopment, ranging from neural differentiation to the formation of functional neuronal networks. This review focuses on the multifaceted involvement of lipid rafts in key neurodevelopmental processes, including neural differentiation, synaptogenesis and myelination. Through the spatial organisation of signalling components, lipid rafts facilitate precise signalling events that determine neural fate during embryonic development and in adulthood. The evolutionary conservation of lipid rafts underscores their fundamental importance for the structural and functional complexity of the nervous system in all species. Furthermore, there is increasing evidence that environmental factors can modulate the composition and function of lipid rafts and influence neurodevelopmental processes. Understanding the intricate interplay between lipid rafts and neurodevelopment not only sheds light on the fundamental mechanisms governing brain development but also has implications for therapeutic strategies aimed at cultivating neuronal networks and addressing neurodevelopmental disorders.

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Section: Structure and Function Of Lipid Raftsmentioning

confidence: 99%

Lipid Rafts: The Maestros of Normal Brain Development

Viljetić,

Blažetić,

Labak

et al. 2024

Biomolecules

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“…Gangliosides play multifaceted roles especially during the neurodevelopmental stage, contributing to the important processes that shape the developing nervous system [37]. Their involvement in neuronal migration, axon guidance, dendritic arborization, synaptogenesis, and myelination highlights their significance in ensuring proper neuronal development and function [38]. Simple gangliosides, such as GM3, are prevalent during early neurodevelopmental stages and are involved in fundamental processes like cell proliferation, migration, and differentiation.…”

Section: Advances In Cell and Gene Therapymentioning

confidence: 99%

Silencing of B4Galnt1 Gene Prevents GM2 Accumulation in Tay-Sachs Cells

Ateş,

İnci,

Demir

et al. 2024

Advances in Cell and Gene Therapy

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Introduction. The Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder resulting from genetic mutations in the HEXA gene encoding the α-subunit of β-hexosaminidase A leading to the accumulation of GM2 ganglioside in the central nervous system. Multiple therapeutical strategies have been investigated such as gene therapy for Tay-Sachs patients; however, there is still no cure. In the present study, we suggest a new approach for the treatment of the Tay-Sachs disease with the concept of substrate reduction therapy by using AAV9-mediated RNAi technology targeting the B4Galnt1 gene at the upstream of the enzymatic defect in TSD pathology to decrease GM2 biosynthesis and accumulation in cell models of TSD. Material and Methods. We employed AAV9-mediated shRNA transduction for mice and human Tay-Sachs cells. After transduction, expression levels of ganglioside metabolism genes were analyzed by RT-PCR and GM2 and lysosome-associated membrane protein 1 (LAMP1) protein levels were evaluated by immunocytochemistry analysis. Results. Here, we have shown that AAV9-shRNA transduction effectively reduced B4Galnt1 expression in TSD cells demonstrating a reduction in GM2 accumulation and LAMP1. Discussion. Our data shows that AAV-mediated B4Galnt1-shRNA transduction can ameliorate disease pathologies by decreasing the lysosomal accumulation of GM2 through selectively reducing B4Gant1 activity in cell models of the Tay-Sachs disease. Therefore, we suggest promising novel experimental therapy for this devastating disease using a mouse model in the future.

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“…Gangliosides represent a class of glycosphingolipids that are mainly located in the outer layer of the plasma membrane and possess remarkable functions in the mammalian central nervous system (CNS) [1][2][3]. A ganglioside molecule encompasses a hydrophilic O-glycan sequence and a hydrophobic lipid part, i.e., the ceramide (Cer) moiety, which contains a sphingoid base and a fatty acid chain.…”

Section: Introductionmentioning

confidence: 99%

Advances in Mass Spectrometry of Gangliosides Expressed in Brain Cancers

Biricioiu,

Sarbu,

Ica

et al. 2024

IJMS

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Gangliosides are highly abundant in the human brain where they are involved in major biological events. In brain cancers, alterations of ganglioside pattern occur, some of which being correlated with neoplastic transformation, while others with tumor proliferation. Of all techniques, mass spectrometry (MS) has proven to be one of the most effective in gangliosidomics, due to its ability to characterize heterogeneous mixtures and discover species with biomarker value. This review highlights the most significant achievements of MS in the analysis of gangliosides in human brain cancers. The first part presents the latest state of MS development in the discovery of ganglioside markers in primary brain tumors, with a particular emphasis on the ion mobility separation (IMS) MS and its contribution to the elucidation of the gangliosidome associated with aggressive tumors. The second part is focused on MS of gangliosides in brain metastases, highlighting the ability of matrix-assisted laser desorption/ionization (MALDI)-MS, microfluidics-MS and tandem MS to decipher and structurally characterize species involved in the metastatic process. In the end, several conclusions and perspectives are presented, among which the need for development of reliable software and a user-friendly structural database as a search platform in brain tumor diagnostics.

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Gangliosides in nervous system development, regeneration, and pathologies

Cited by 15 publications

References 109 publications

Lipid Rafts: The Maestros of Normal Brain Development

Lipid Rafts: The Maestros of Normal Brain Development

Silencing of B4Galnt1 Gene Prevents GM2 Accumulation in Tay-Sachs Cells

Advances in Mass Spectrometry of Gangliosides Expressed in Brain Cancers

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