The role of Sphingolipids in myelination and myelin stability and their involvement in childhood and adult demyelinating disorders

Giussani, Paola; Prinetti, Alessandro; Tringali, Cristina

doi:10.1111/jnc.15133

Cited by 53 publications

(33 citation statements)

References 116 publications

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“…Furthermore, satellite glia specifically expressed genes involved in mitochondrial beta-oxidation ( Acaa2, Acadl, Acadm, Acsbg1, Eci1 ) ( Figure 2D, Table S1 ), which produces energy from fatty acids (Barber and Raben, 2019). Schwann cells were strongly enriched for genes involved in myelination (Figure 2E), including genes specific for sphingolipid synthesis ( Fa2h, Samd8, Sptlc2, Ugt8a ) ( Table S1 ), which are abundant myelin components in both central and peripheral nervous systems (Giussani et al, 2021). Schwann cells also expressed fatty acid elongase genes ( Elovl1, Elovl7 ) that were distinct from those expressed in satellite glia ( Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

Diversity of satellite glia in sympathetic and sensory ganglia

Mapps

Thomsen

Boehm

et al. 2021

Preprint

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Satellite glia are the major glial type found in ganglia of the peripheral nervous system and wrap around cell bodies of sympathetic and sensory neurons that are very diverse. Other than their close physical association with peripheral neurons, little is known about this glial population. Here, we performed single cell RNA sequencing analysis and identified five different populations of satellite glia from sympathetic and sensory ganglia. We identified three shared populations of satellite glia enriched in immune-response genes, immediate-early genes and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Further, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals remarkable heterogeneity of satellite glia in the peripheral nervous system.

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Section: Resultsmentioning

confidence: 99%

Diversity of satellite glia in sympathetic and sensory ganglia

Mapps

Thomsen

Boehm

et al. 2021

Preprint

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“…Sphingolipids are widely distributed in the organism, including the central and peripheral nervous system [7,8]. The closest association of sphingolipids with neurodegenerative diseases was related to their structural function, especially the glycosphingolipids, as the main component of the plasma membrane of oligodendrocytes and myelin [9]. However, several studies have demonstrated the implication of sphingolipids in several key biological processes such as cellular proliferation and migration, differentiation, autophagy, apoptosis, senescence, and inflammation [8,[10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Ceramide Metabolism and Parkinson’s Disease—Therapeutic Targets

et al. 2021

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Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson’s disease.

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“…It is caused by multiple genetic alterations in the gene encoding for the enzyme galactosylceramidase (GALC; EC 3.2.1.46) or, in some rare cases, for the Sphingolipid activator protein saposin A (SapA) [ 1 ]. The deficiency of GALC or SapA does not allow the proper functioning of the complex sphingolipid cell pathway, which is especially crucial for myelinating cells [ 2 ]. More specifically, the GALC-SapA complex is also responsible for cleaving the glycosydic linkage of galatosylsphingosine (psychosine or PSY), a highly cytotoxic molecule which is able to insert into the cell membrane, disrupt raft architecture, and presumably deregulate multiple cell signaling cascades [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Visual System Impairment in a Mouse Model of Krabbe Disease: The Twitcher Mouse

et al. 2020

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Krabbe disease (KD, or globoid cell leukodystrophy; OMIM #245200) is an inherited neurodegenerative condition belonging to the class of the lysosomal storage disorders. It is caused by genetic alterations in the gene encoding for the enzyme galactosylceramidase, which is responsible for cleaving the glycosydic linkage of galatosylsphingosine (psychosine or PSY), a highly cytotoxic molecule. Here, we describe morphological and functional alterations in the visual system of the Twitcher (TWI) mouse, the most used animal model of Krabbe disease. We report in vivo electrophysiological recordings showing defective basic functional properties of the TWI primary visual cortex. In particular, we demonstrate a reduced visual acuity and contrast sensitivity, and a delayed visual response. Specific neuropathological alterations are present in the TWI visual cortex, with reduced myelination, increased astrogliosis and microglia activation, and around the whole brain. Finally, we quantify PSY content in the brain and optic nerves by high-pressure liquid chromatography-mass spectrometry methods. An increasing PSY accumulation with time, the characteristic hallmark of KD, is found in both districts. These results represent the first complete characterization of the TWI visual system. Our data set a baseline for an easy testing of potential therapies for this district, which is also dramatically affected in KD patients.

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The role of Sphingolipids in myelination and myelin stability and their involvement in childhood and adult demyelinating disorders

Cited by 53 publications

References 116 publications

Diversity of satellite glia in sympathetic and sensory ganglia

Diversity of satellite glia in sympathetic and sensory ganglia

Ceramide Metabolism and Parkinson’s Disease—Therapeutic Targets

Visual System Impairment in a Mouse Model of Krabbe Disease: The Twitcher Mouse

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