The potential role for sphingolipids in neuropathogenesis of Alzheimer’s disease

Alessenko, A. V.

doi:10.18097/pbmc20135901025

Cited by 15 publications

(7 citation statements)

References 92 publications

(149 reference statements)

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“…Dihydrosphingosine, hexadecasphinganine, and phytosphingosine are classified as sphingolipids [41] . The central nervous system contains large amounts of sphingolipids; their metabolites play not only a structural role in biomembranes, but also act as second messengers involved in the transduction of numerous cell signals [42] . There is also strong evidence that cholesterol and sphingomyelin preferentially interact with each other in neuronal membranes, and that this interaction has a direct effect on the structure and permeability of the cell membrane and second-messenger systems [43] .…”

Section: Discussionmentioning

confidence: 99%

A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease

Liu

et al. 2016

Journal of Ginseng Research

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BackgroundAlzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated.MethodsUltra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively.ResultsThe impaired cognitive function and increased hippocampal Aβ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice.ConclusionThese results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.

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Section: Discussionmentioning

confidence: 99%

A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease

Liu

et al. 2016

Journal of Ginseng Research

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“…These effects can reduce a number of brain synapses and might cose memory disorders in early stages of AD [48]. Furthermore, agents that inhibit acetylcholinesterase (e.g., rivastigmine) modulated plasma phospholipid profile decreasing choline-containing phospholipids level [49].…”

Section: Total Level Of Phospholipids and Level Of Individual Phosphomentioning

confidence: 99%

Preventive effect of N-stearoylethanolamine on memory disorders, blood and brain biochemical parameters in rats with experimental scopolamine-induced cognitive impairment

Horid’ko¹,

Kosiakova²,

Berdyshev³

2018

Ukr.Biochem.J

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The impairment of cognitive functions is the most studied medical and social problem nowadays. The aim of this study was to evaluate the protective effects of n-stearoylethanolamine (nSe) on memory state, blood and brain biochemical parameters in rats under scopolamine-induced cognitive impairment. The results of this study shown that nSe administration to rats per os (5 mg/kg, 5 days, during last 3 days nSe was administrated 20 min prior to scopolamine injection (1 mg/kg, once daily for 3 days, intraperitoneally)) prevented the development of memory impairment. In particular, NSe action was associated with the prevention of increase in acetylcholinesterase activity, changes in phospholipid, free and esterified cholesterol level in hippocampus and frontal cortex, and disruption in pro-/antioxidant balance in blood and studied brain sections. considering the above mentioned biological effects, nSe is a promising drug candidate for integrative therapy of cognitive impairment of different profiles.

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“…Most glycerophospholipids were upregulated in the M1 group compared with the resting group, and the sphingolipids and glycerophospholipids of intracellular were increased compared with the M2 group. Sphingolipid metabolites not only play a structural role in biomembranes but also act as second messengers involved in the transduction of numerous cell signals (Alessenko, ). Excessive accumulation of sphingolipids causes macrophage activation and inflammation.…”

Section: Resultsmentioning

confidence: 99%

Metabolic responses of BV‐2 cells to puerarin on its polarization using ultra‐performance liquid chromatography–mass spectrometry

Wang

et al. 2020

Biomedical Chromatography

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Microglia are the primary immune cells in the central nervous system with functional plasticity. They can be activated into M1 and M2 phenotypes when neuroinflammation‐related diseases occur. M1 phenotype cells produce pro‐inflammatory mediators that cause neuroinflammation and the M2 phenotype can secrete anti‐inflammatory cytokines that protect neurons from damage. Therefore, inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for treating neuroinflammation‐related diseases. Puerarin has been demonstrated to exert anti‐inflammatory and neuroprotective effects. However, the role of puerarin in regulating microglia polarization and its reaction mechanism has not been fully elucidated. In this paper, a metabolomics approach with ultra‐performance liquid chromatography–mass spectrometry was performed to investigate the metabolic changes of BV‐2 cells in different phenotypes and test the effects of puerarin on polarization. Thirty‐nine metabolites were identified as the biomarkers related to the polarization of BV‐2 cells and puerarin intervention reverted the content of most of the biomarkers. Our study demonstrated that puerarin could play a key role in M1/M2 polarization of BV‐2 cells from a perspective of metabolomics, and it could regulate the balance between promotion and suppression of inflammation.

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The potential role for sphingolipids in neuropathogenesis of Alzheimer’s disease

Cited by 15 publications

References 92 publications

A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease

A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease

Preventive effect of N-stearoylethanolamine on memory disorders, blood and brain biochemical parameters in rats with experimental scopolamine-induced cognitive impairment

Metabolic responses of BV‐2 cells to puerarin on its polarization using ultra‐performance liquid chromatography–mass spectrometry

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