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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).
Genetic Control of Endotoxin Responsiveness: The Lps Gene Revisited
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Stefanie N. Vogel, Nayantara Bhat, Danielle Malo, Salman T. Qureshi
Ceramide is a lipid second messenger that is principally generated by the hydrolysis of membrane sphingomyelin by sphingomyelinases. Because of its lipid nature, the interaction of ceramide with specific signaling pathways is strictly membrane associated (reviewed in Ref. 61). Ceramide-activated intracellular signaling involves a cytosolic ceramide-activated protein phosphatase (62) and a membrane-associated, ceramide-activated protein (CAP) kinase. CAP kinase has been postulated to initiate TNF-α-induced signaling by phosphorylating and activating Raf-1 and was recently demonstrated to be identical to “kinase suppressor of Ras” (KSR) (63). On the basis of structural similarities between lipid A and ceramide, Joseph et al. (64) postulated that LPS might activate the ceramide-activated kinase directly, in the absence of sphingomyelinase activity, by mimicking the second-messenger function of ceramide.
Utilization of PEGylated cerosomes for effective topical delivery of fenticonazole nitrate: in-vitro characterization, statistical optimization, and in-vivo assessment
Published in Drug Delivery, 2021
Rofida Albash, Carol Yousry, Abdulaziz Mohsen Al-Mahallawi, Ahmed Adel Alaa-Eldin
Ceramides are the simplest and the most hydrophobic type of sphingolipids, which are responsible for the barrier function of the stratum corneum (SC). Ceramides represent 50% of the lipid weight of the SC, however, they are present in a much lower proportion in cell membranes (Khazanov et al., 2008). Some reports support that ceramide-containing formulations, at an optimum concentration of 0.05% w/w; may aid in the renewal of the skin’s natural protective layer and formation of an effective barrier against moisture loss. This is particularly suitable for long-term protection and repair of sensitive and dry skin (Su et al., 2017). Several studies have been devoted to identify the different types of ceramides present in the human skin and their functionwhere they reported that alterations in ceramide content are associated with many skin diseases such as atopic dermatitis, psoriasis and topical fungal infections (Meckfessel & Brandt, 2014). A study conducted on mice showed that ceramide was essential for their survival. Mice deficient in ceramide died shortly after birth as a result of trans-epidermal water loss. Cultured skin from mice was also more susceptible to colonization by Candida albicans, emphasizing the importance of skin barrier function to protect against foreign insults (Jennemann et al., 2012).
The effect of portulaca oleracea alkaloids on antidiabetic properties through changes in ceramide metabolism
Published in Egyptian Journal of Basic and Applied Sciences, 2021
Hanie roozi, Masuod Mashhadi Akbar Boojar, Akram Eidi, Ramezanali Khavari-Nejad
The present study results demonstrated that as major isoquinoline alkaloids in Portulaca oleracea, low to moderate concentrations of both OL-E and OL-L have a considerable stimulating effect on insulin secretion and improving glucose uptake. These findings are in accordance with the results of other related investigations. The important point is that a high dose of Oleracein derivative is associated with increasing the ceramide generation and cellular toxicity and decreasing insulin secretion. Consequently, OL-E and OL-L can be recommended as a potential natural antidiabetic agent in preventing or treating DM and its multiple complications. Nevertheless, it should be regarded that the excessive consumption of these compounds may result in inconsistent and undesirable responses with possible involvement of the ceramide pathway. Further studies are recommended to augment and confirm our suggestions.
CERKL mutation causing retinitis pigmentosa(RP) in Indian population – a genotype and phenotype correlation study
Published in Ophthalmic Genetics, 2020
Parveen Sen, Puja Maitra, Srikrupa Natarajan, Srivatsan Sripriya, Sinnakaruppan Mathavan, Muna Bhende, Pradeep T Manchegowda
“CERKL” gene encodes ceramide kinase like protein, which is a homologue of ceramide kinase (CERK) that aids conversion of ceramide to ceramide 1 phosphate. Ceramide is a metabolic product of sphingophospholipids which is a constituent of cell membrane and participates in intracellular signalling and apoptosis (12). In lower animals CERKL is expressed in Ganglion cell layer (GCL) and lesser extent in Outer nuclear layer (ONL) and Inner nuclear layer (INL). The evidence of CERKL acting as an anti-apoptotic agent links its role in diseases concerning photoreceptors loss. (13) There is increasing evidence that CERKL gene, through its role in sphingophospholipid and ceramide metabolism, protects the photoreceptors from oxidative stress and without a properly functioning CERKL the photoreceptors are prone to apoptosis causing severe rod and cone degeneration. (14)