Abnormal Sphingolipid World in Inflammation Specific for Lysosomal Storage Diseases and Skin Disorders

Moskot, Marta; Bocheńska, Katarzyna; Jakóbkiewicz‐Banecka, Joanna; Banecki, Bogdan; Gabig-Cimińska, Magdalena

doi:10.3390/ijms19010247

Cited by 31 publications

(24 citation statements)

References 201 publications

(235 reference statements)

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“…Another theory of LysoGb3 accumulation in neuronopathic forms of MPSs may be the relationship between lactosylceramide (LacCer) and globotriaosylceramide (Gb3) ( Figure 5). There is evidence that LacCer accumulates in MPS II and III [16,17], and it is the main core of most gangliosides [18]. It is also reported that LacCer is one of the main accumulated components in the brain samples of patients with neurological forms of MPSs; however, a significant increase of Gb3 was not fixed [19].…”

Section: Discussionmentioning

confidence: 99%

Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses

et al. 2020

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Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders associated with impaired glycosaminoglycans (GAGs) catabolism. In MPS I, II, III, and VII, heparan sulfate (HS) cannot be degraded because of the lack of sufficient activity of the respective enzymes, and its accumulation in the brain causes neurological symptoms. Globotriaosylsphingosine (LysoGb3), the deacylated form of globotriaosylceramide (Gb3), is described as a highly sensitive biomarker for another lysosomal storage disease-Fabry disease. The connection between MPSs and LysoGb3 has not yet been established. This study included 36-MPS I, 15-MPS II, 25-MPS III, 26-MPS IV, and 14-MPS VI patients who were diagnosed by biochemical and molecular methods and a control group of 250 males and 250 females. The concentration of lysosphingolipids (LysoSLs) was measured in dried blood spots by high pressure liquid chromatography-tandem mass spectrometry. We have demonstrated that LysoGb3 concentration was significantly elevated (p < 0.0001) in untreated MPS I (3.07 + 1.55 ng/mL), MPS II (5.24 + 2.13 ng/mL), and MPS III (6.82 + 3.69 ng/mL) patients, compared to the control group (0.87 + 0.55 ng/mL). LysoGb3 level was normal in MPS VI and MPS IVA (1.26 + 0.39 and 0.99 + 0.38 ng/mL, respectively). Activity of α-galactosidase A (α-Gal A), an enzyme deficient in Fabry disease, was not, however, inhibited by heparan sulfate in vitro, indicating that an increase of LysoGb3 level in MPS I, MPS II, and MPS III is an indirect effect of stored MPSs rather than a direct result of impairment of degradation of this compound by HS. Our findings indicate some association of elevated LysoGb3 concentration with the neuronopathic forms of MPSs. The pathological mechanism of which is still to be studied.

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Section: Discussionmentioning

confidence: 99%

Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses

et al. 2020

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“…15,16 Simultaneous disturbances in ceramide levels in skin lesions and blood of affected patients was detected in only one study but this was only observed in severe and not mild or moderate psoriasis. 17 Other recent studies detected a decrease in serum plasma levels of ceramide in patients compared to healthy controls. On the contrary, one report detected increased levels of ceramide in both lesional skin as well as in blood of patients compared to controls.…”

Section: Discussionmentioning

confidence: 92%

Therapeutic implications and role of serum sphingolipids on psoriasis severity after narrow band ultraviolet B treatment: A cross sectional controlled study

Nada

Elshabrawy

Ismail

et al. 2020

Dermatologic Therapy

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Sphingolipids (SLs), are structural components of the skin that contribute to the regulation of the proliferation and differentiation of keratinocytes as well as regulation of the skin epidermal barrier. A prospective cross sectional comparative controlled study was designed to evaluate the serum level of sphingosine 1 phosphate (S1P) and ceramide (CER) before and after narrow band ultraviolet B (NBUVB) in psoriatic patients. The study included 32 patients presented with psoriasis and 32 healthy age and sex matched control volunteers. (S1P and CER) levels were measured before and after NBUVB sessions for psoriatic patients and their levels were correlated to psoriasis area and severity index (PASI) improvements. PASI scores and serum values of the studied sphingolipids demonstrated a significant difference between the baseline and at the end of the 12 weeks NBUVB treatment. A statistically significant positive correlation was established between psoriasis severity and S1P serum levels before and after treatment while no correlation was observed between psoriasis severity and CER serum levels. Decreased total CER and increased S1P serum levels reflect altered sphingolipid metabolism in psoriasis and can be predictors of disease severity.

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“…Cantuti et al reported abnormal expression of caspase 3 in presynaptic terminals of the twitcher mouse, which underlines the possibility that exacerbated degradation of synaptic components by caspase activities impact on nerve transmission (Cantuti-Castelvetri et al, 2015 ). Considering that inflammation of the nerve tissue is an integral part of the cellular response in most neurological LSDs (Moskot et al, 2018 ), the activation of microglia, inflammation, and cell death pathways are likely to influence synaptic function in these diseases and contribute to some of the neurobehavioral manifestations observed in patients.…”

Section: Inflammation As a Contributor To Synaptic Failure In Lsdsmentioning

confidence: 99%

Synaptic Function and Dysfunction in Lysosomal Storage Diseases

Rebiai

Givogri

Gowrishankar

et al. 2021

Front. Cell. Neurosci.

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Lysosomal storage diseases (LSDs) with neurological involvement are inherited genetic diseases of the metabolism characterized by lysosomal dysfunction and the accumulation of undegraded substrates altering glial and neuronal function. Often, patients with neurological manifestations present with damage to the gray and white matter and irreversible neuronal decline. The use of animal models of LSDs has greatly facilitated studying and identifying potential mechanisms of neuronal dysfunction, including alterations in availability and function of synaptic proteins, modifications of membrane structure, deficits in docking, exocytosis, recycling of synaptic vesicles, and inflammation-mediated remodeling of synapses. Although some extrapolations from findings in adult-onset conditions such as Alzheimer’s disease or Parkinson’s disease have been reported, the pathogenetic mechanisms underpinning cognitive deficits in LSDs are still largely unclear. Without being fully inclusive, the goal of this mini-review is to present a discussion on possible mechanisms leading to synaptic dysfunction in LSDs.

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Abnormal Sphingolipid World in Inflammation Specific for Lysosomal Storage Diseases and Skin Disorders

Cited by 31 publications

References 201 publications

Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses

Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses

Therapeutic implications and role of serum sphingolipids on psoriasis severity after narrow band ultraviolet B treatment: A cross sectional controlled study

Synaptic Function and Dysfunction in Lysosomal Storage Diseases

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