Plasma sphingolipid abnormalities in neurodegenerative diseases

Oizumi, Hideki; Sugimura, Yukinobu; Totsune, Tomoko; Kawasaki, Iori; Ohshiro, Saki; Baba, Toru; Kimpara, Teiko; Sakuma, Hiroaki; Hasegawa, Takafumi; Kawahata, Ichiro; Fukunaga, Kohji; Takeda, Atsushi

doi:10.1371/journal.pone.0279315

Cited by 17 publications

(13 citation statements)

References 80 publications

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“…Therefore, we are interested in determining whether RBCs contribute to the AD pathogenesis. Previous studies have reported decreased S1P levels in AD tissues and plasma [39,40]. S1P protects neuronal cells from apoptosis [41], notably in response to A [42].…”

Section: Introductionmentioning

confidence: 89%

Sphingosine-1-Phosphate Decreases Erythrocyte Dysfunction Induced by Beta-Amyloid

Misiti,

Diotaiuti,

Lombardo

et al. 2024

Preprint

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Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

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Section: Introductionmentioning

confidence: 89%

Sphingosine-1-Phosphate Decreases Erythrocyte Dysfunction Induced by Beta-Amyloid

Misiti,

Diotaiuti,

Lombardo

et al. 2024

Preprint

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“…In vivo studies suggest that osteopontin (CSF and blood) [97,98], serpins (CSF and blood) [85], sphingolipids and lysophospholipids (blood) [99], and serum amyloid A (CSF) [76] are altered in LBD disease cohorts compared to controls and therefore may have neurobiological relevance to LBD, or at least neurodegeneration more broadly. Protein glycosylation profiles might predict conversion to DLB versus PD clinical disease in people with idiopathic REM sleep disorder [32].…”

Section: Other Inflammatory Molecules Measured Postmortem and In Vivomentioning

confidence: 99%

“…Blood levels of cytokines, and possibly other biomarkers of interest, are affected by diurnal variation [157]. Only a handful of identified studies, however, report standardizing collection time, with samples for inflammatory molecule analysis taken in the morning or fasted (likely a morning sample) [33,62,67,72,76,78,[99][100][101]156]. As mentioned above, the sensitivity of the assays used may be too low to detect molecules of interest, particularly when comparing older studies to those using more advanced detection methods or comparing different assay platforms; therefore, conclusions that can be drawn about their absence are limited [158,159].…”

Section: Limitations Of In Vivo Studiesmentioning

confidence: 99%

Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review

Loveland,

Yu,

Churilov

et al. 2023

IJMS

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Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson’s disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.

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“…This lipid species is related to the metabolic pathway of glucosylceramide, which is linked to PD [ 209 ]. Another study used LC-MS/MS to evaluate plasma lipidomics in individuals with different neurodegenerative diseases, including idiopathic PD, dementia with LB and multiple system atrophy, as synucleinopathies, and Alzheimer’s disease and progressive supranuclear palsy, as tauopathies [ 228 ]. In this study, the authors found that the plasma levels of sphingosine-1-phosphate (which seems to have a neuroprotective role against aggregate formation) were lower, and those of monohexylceramide and lactosylceramide (which seem to be involved in neuroinflammation and neuronal cell death) were higher in the neurodegenerative disease groups, compared with the healthy controls, supporting the idea that abnormal sphingolipid metabolism has a key role in neurodegeneration [ 228 ].…”

Section: Lipidomics As a New Tool To Identify Biomarkers In Parkinson...mentioning

confidence: 99%

New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics

et al. 2023

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Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract (mainly constipation), which start much earlier than the motor symptoms. Remarkably, current treatments only reduce motor symptoms, not without important drawbacks (relatively low efficiency and impactful side effects). Thus, new approaches are needed to halt PD progression and, possibly, to prevent its development, including new therapeutic strategies that target PD etiopathogeny and new biomarkers. Our aim was to review some of these new approaches. Although PD is complex and heterogeneous, compelling evidence suggests it might have a gastrointestinal origin, at least in a significant number of patients, and findings in recently developed animal models strongly support this hypothesis. Furthermore, the modulation of the gut microbiome, mainly through probiotics, is being tested to improve motor and non-motor symptoms and even to prevent PD. Finally, lipidomics has emerged as a useful tool to identify lipid biomarkers that may help analyze PD progression and treatment efficacy in a personalized manner, although, as of today, it has only scarcely been applied to monitor gut motility, dysbiosis, and probiotic effects in PD. Altogether, these new pieces should be helpful in solving the old puzzle of PD.

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Plasma sphingolipid abnormalities in neurodegenerative diseases

Cited by 17 publications

References 80 publications

Sphingosine-1-Phosphate Decreases Erythrocyte Dysfunction Induced by Beta-Amyloid

Sphingosine-1-Phosphate Decreases Erythrocyte Dysfunction Induced by Beta-Amyloid

Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review

New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics

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