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Insulin Resistance as a Risk Factor for Alzheimer's Disease
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Miren Ettcheto, Amanda Cano, Elena Sanchez-Lopez, Carme Auladell, Jaume Folch, Antoni Camins
Ceramides comprise a family of sphingolipids that are generated from fatty acids and sphingosine. It is well known that ceramides play an important role in the structure of the cell membrane since they participate in the formation of the lipid raft. On the other hand, ceramides exert various physiological and regulatory effects on cell signalling pathways that mediate cellular growth, proliferation and senescence, among other functions (58). Interestingly, ceramides like other neurotoxic lipids can cross the BBB, contributing to the BIR and neurodegeneration. In this line, previous studies have reported that ceramide levels increase in the brain of preclinical mice models of AD and in LOAD patients (143). Likewise, ceramides exert a role in LOAD pathophysiology promoting the regulation of BACE1 and the generation and aggregation of Aβ (144, 145). Besides, ceramides which are located especially in the myelin sheath that surrounds some nerve cell axons, have also been observed in plasma, CSF and brain tissue of LOAD patients, and have also been associated with an increase in Aβ plaques (146, 147).
Macronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Sphingolipids constitute a class of lipids defined by their 18 carbon-amino-alcohol backbones which are synthesized in the endoplasmic reticulum from non-sphingolipid precursors (66, 117). In sphingolipids, glycerol is replaced by a group of aliphatic amino alcohol named sphingosine that contains two alcohols with the middle position occupied by an amine. Sphingolipids are complex lipids which yield fatty acids, sphingosine, phosphoric acid, and an alcohol component upon hydrolysis. A sphingosine has three parts, a three carbon chain with two alcohols and amine attached and a long hydrocarbon chain containing 12–22 carbon atoms (69, 115, 117). The main and abundant component of sphingolipids in animals is sphingomyelin that constitutes the membranous myelin sheath surrounding nerve cell axons (114, 117). Sphingomyelin usually consists of a sphingosine linked to a long chain fatty acyl chain called ceramide and attached to a phosphocholine group at the primary alcohol group of a sphingosine (66, 117). Precisely, ceramide is amide of fatty acids with sphingosine. So, sphingomyelin can also be classified as sphingophospholipid (115). Like glycerophospholipids and cholesterol, sphingolipids are ubiquitous in the body and found in every cell membrane, particularly nerve cells and brain tissues (114–117).
Immune Responses Regulated by Exosomal Mechanisms in Cardiovascular Disease
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Brooke Lee, Ioannis D. Kyriazis, Ruturaj Patil, Syed Baseeruddin Alvi, Amit Kumar Rai, Mahmood Khan, Venkata Naga Srikanth Garikipati
EVs can bind to specific receptors on a target cell, where they then fuse with the cell membrane. Suppose the target cell is an antigen-presenting cell (APC); in that case, the EVs’ components will be degraded and taken up by the complement system, which then binds to receptors of specific major histocompatibility complexes (MHCs), either class I or class II (Kowal, Arras et al. 2016; Garikipati, Shoja-Taheri et al. 2018). This function is driven by a well-orchestrated, but complicated cascade of signaling pathways that initiate an adequate immune system response against the presented proteins by MHC class I or II (Raposo and Stoorvogel 2013). The specific location of the lumen’s inward budding depends on the endosomal sorting complex required for transport (ESCRT), which is composed of proteins Hrs, Tsg101, Alix, and Vsg4. This protein collection selects which surface proteins will be taken in by the cell in order to form an early endosome (Trajkovic, Hsu et al. 2008). Ceramides are formed in microdomains with upregulated sphingolipids, and they are essential to induce the budding of EVs (Gulbins and Kolesnick 2003). Limited information exists concerning the EVs’ function despite an understanding of their biogenesis, and the current methods used to characterize them are specific and time-consuming.
Systematic review on activity of liposomal encapsulated antioxidant, antibiotics, and antiviral agents
Published in Journal of Liposome Research, 2022
Reshna K. R, Preetha Balakrishnan, Sreerag Gopi
Phospholipid contains two major categories including glycerophospholipids and sphingolipids (categorized into sphingomyelin and glycolipid). The glycerophospholipids are considered as a backbone of liposome. The chemical structure of glycerophospholipids consists of a hydrophilic head group and a hydrophobic side chain. Different glycerophospholipids are obtained as a result of head group variation, for example, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA), phosphatidylglycerol (PG), and cardiolipin (CL). Decreased nonpolar moieties with varying lengths produce a wide range of different glycerophospholipids, such as dimyristoyl, dipalmitoyl, and distearoyl PC, among others. Furthermore, the type of bond formed between glycerol and aliphatic chains (ether or ester) results in the formation of distinct glycerophospholipids.
Emerging role of metabolomics in protein conformational disorders
Published in Expert Review of Proteomics, 2021
Nimisha Gupta, Sreelakshmi Ramakrishnan, Saima Wajid
Chang et al. (2017) demonstrated that the plasma levels of kynurenic acid were higher in PD patients than in HD patients and controls as seen using the validation cohort [100]. Similar studies were conducted in AD patients when variations in levels of fatty acids and acyl-carnitines were found [101]. Mischley et al. (2016) reported correlations between glutathione status, age, and disease severity. They observed that the concentration of whole blood glutathione has a significant correlation with disease severity and may be useful as a biomarker for PD progression [102]. Many studies have indicated perturbations in fatty acid and cholesterol metabolism, considered to be a common metabolite variation in AD, PD, and HD [103,104]. Sphingolipids were found to be altered in PD, AD, and HD. Recently, several studies have shown that alterations in sphingolipid metabolism and their related signaling pathways are shared with various neurodegenerative disorders and may contribute to their complex pathogenesis. Additionally, ceramide and S1P (bioactive sphingolipids) are being implicated as potential therapeutic targets in different neurodegenerative disorders [105].
Antiproliferative Effects of Thymoquinone in MCF-7 Breast and HepG2 Liver Cancer Cells: Possible Role of Ceramide and ER Stress
Published in Nutrition and Cancer, 2021
Mutay Aslan, Ebru Afşar, Esma Kırımlıoglu, Tuğçe Çeker, Çağatay Yılmaz
A significant increase was observed in cellular levels of C16-C24 CERs in MCF-7 and HepG2 cells treated with toxic doses of TQ for 24 h, compared to controls (Tables 1 and 2). Our results support a previous study that has shown that TQ triggers suicidal death of blood platelets possibly through an effect paralleled by increase of ceramide formation (13). We have also observed that incubation with 100 and 200 µM TQ for 24 h, significantly decreased S1P and C1P levels in MCF-7and HepG2 cells, respectively. To our knowledge, this is the first study to report decreased levels of S1P and C1P in cancer cells treated with TQ. Biologically active sphingolipids have important roles in the operation of several vital biological functions that are fundamental to cancer pathogenesis. Latest considerable advance in knowledge of biologically active sphingolipid synthesis, particularly within ceramide and S1P-mediated pathways, has identified central roles for these molecules both in cancer development and progression. Ceramide, a chief molecule in sphingolipid metabolism, operationally functions as a tumor-suppressor lipid, triggering antiproliferative and apoptotic reactions in various cancer cells (22). Quite the reverse, S1P and C1P induces responses that, on combination, make S1P and C1P a tumor-promoting lipid. These findings are paving the way for the progression of anticancer therapies (23).