The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid β Aggregation

Rudajev, Vladimı́r; Novotný, Jiřı́

doi:10.3390/membranes10090226

Cited by 34 publications

(28 citation statements)

References 182 publications

(317 reference statements)

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“… 48 A recent study by Vladimir Rudajev reported that sphingomyelin triggers oligomerization of Aβ40, which is one of the major biochemical hallmarks of Alzheimer’s disease. 49 In addition, previous lipidomics studies performed on the brains of wild-type mice at different ages revealed that the content of glucosylceramide, glucosylsphingosine, and GM1a was increased with aging. 50 In the present study, SM (d18:1/18:0) and glucosylceramide were significantly decreased after treatment with S. baicalensis compared with the normal cohort, and supporting evidence was also obtained for the serum levels of these lipids after treatment with Huang-Lian-Jie-Du-Tang.…”

Section: Discussionmentioning

confidence: 96%

Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics

Ge¹,

Qi²,

Qu³

et al. 2021

DDDT

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Background S. baicalensis , a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer’s disease. Aim of the Study To elucidate the mechanism by which S. baicalensis modulates lipid metabolism and explore the medicinal effects of S. baicalensis at a holistic level. Materials and Methods The potential active ingredients of S. baicalensis and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after S. baicalensis treatment in order to identify significantly altered metabolites, and crucial targets and compounds were validated by molecular docking. Results Steroid biosynthesis, sphingolipid metabolism, the PPAR signaling pathway and glycerolipid metabolism were enriched and predicted to be potential pathways upon which S. baicalensis acts. Further metabolomics assays revealed 14 significantly different metabolites were identified as lipid metabolism-associated elements. After the pathway enrichment analysis of the metabolites, cholesterol metabolism and sphingolipid metabolism were identified as the most relevant pathways. Based on the results of the pathway analysis, sphingolipid and cholesterol biosynthesis and glycerophospholipid metabolism were regarded as key pathways in which S. baicalensis is involved to regulate lipid metabolism. Conclusion According to our metabolomics results, S. baicalensis may exert its therapeutic effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways. Upon further analysis of the altered metabolites in certain pathways, agents downstream of squalene were significantly upregulated; however, the substrate of SQLE was surprisingly increased. By combining evidence from molecular docking, we speculated that baicalin, a major ingredient of S. baicalensis , may suppress cholesterol biosynthesis by inhibiting SQLE and LSS, which are important enzymes in the cholesterol biosynthesis pathway. In summary, this study provides new insights into the therapeutic effects of S. baicalensis on lipid metabolism using network pharmacology and lipidomics.

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Section: Discussionmentioning

confidence: 96%

Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics

Ge¹,

Qi²,

Qu³

et al. 2021

DDDT

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“…GM1 in lipid rafts mediate the pathophysiology of several cellular processes, including development, differentiation, and protection of neuronal tissue. GM1 has been proposed to play a negative role in Alzheimer’s disease by changing spatial organization of extracellular amyloid β [ 5 ].…”

Section: Lipid Raftsmentioning

confidence: 99%

Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer

Codini

Garcia‐Gil

Albi

2021

IJMS

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Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies.

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“…It has been also reported that the lipid composition of membranes may modulate the cellular response to the toxic action of amyloid aggregates, thus explaining the different vulnerability of different cell types to amyloid species [ 95 ]. In particular, the importance of GM1, a major component of “lipid-rafts”, in the cellular membranes [ 96 ] as a mediator of amyloid toxicity has been widely documented [ 93 , 96 , 97 , 98 ].…”

Section: Functional Commonalitiesmentioning

confidence: 99%

Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity

Diociaiuti

Bonanni

Cariati

et al. 2021

IJMS

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It has been proposed that a “common core” of pathologic pathways exists for the large family of amyloid-associated neurodegenerations, including Alzheimer’s, Parkinson’s, type II diabetes and Creutzfeldt–Jacob’s Disease. Aggregates of the involved proteins, independently from their primary sequence, induced neuron membrane permeabilization able to trigger an abnormal Ca2+ influx leading to synaptotoxicity, resulting in reduced expression of synaptic proteins and impaired synaptic transmission. Emerging evidence is now focusing on low-molecular-weight prefibrillar oligomers (PFOs), which mimic bacterial pore-forming toxins that form well-ordered oligomeric membrane-spanning pores. At the same time, the neuron membrane composition and its chemical microenvironment seem to play a pivotal role. In fact, the brain of AD patients contains increased fractions of anionic lipids able to favor cationic influx. However, up to now the existence of a specific “common structure” of the toxic aggregate, and a “common mechanism” by which it induces neuronal damage, synaptotoxicity and impaired synaptic transmission, is still an open hypothesis. In this review, we gathered information concerning this hypothesis, focusing on the proteins linked to several amyloid diseases. We noted commonalities in their structure and membrane activity, and their ability to induce Ca2+ influx, neurotoxicity, synaptotoxicity and impaired synaptic transmission.

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The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid β Aggregation

Cited by 34 publications

References 182 publications

Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics

Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics

Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer

Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity

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