Principles of bioactive lipid signalling: lessons from sphingolipids

Hannun, Yusuf A.; Obeid, Lina M.

doi:10.1038/nrm2329

Cited by 2,927 publications

(3,034 citation statements)

References 117 publications

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“…In conclusion, these studies suggest that cholesterol plays an important role in Aβ production by altering the levels of BACE1 in lipid rafts. Beyond cholesterol, some other lipids such as sphingolipids, isoprenoids, and phospholipids also play important roles in Aβ production (Hannun & Obeid, 2008; Hooff, Wood, Muller, & Eckert, 2010; Petanceska & Gandy, 1999). …”

Section: Lifestyle Associations and Interventions For Aging And Admentioning

confidence: 99%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.

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Section: Lifestyle Associations and Interventions For Aging And Admentioning

confidence: 99%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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“…Ceramide is generated by (i) sphingomyelinases [30, 64, 65], (ii) by a de novo synthase pathway [30, 65], (iii) by a retrograde activity of the enzyme ceramidase that mediates the synthesis of ceramide from sphingosine [66], (iv) by the hydrolysis of complex glycosylated lipids [67] and (v) by hydrolysis of ceramide 1-phosphate [68]. Sphingomyelinases hydrolyse sphingomyelin to release ceramide.…”

Section: Sphingomyelinasesmentioning

confidence: 99%

“…Mammalian cells express one gene for the acid sphingomyelinase, which can be targeted to lysosomes or for secretion into secretory lysosomes depending on the glycosylation pattern of the protein [69, 70]. Mammalian cells express at least two different neutral sphingomyelinases and one alkaline sphingomyelinase [65]. …”

Section: Sphingomyelinasesmentioning

confidence: 99%

The Role of Sphingolipids and Ceramide in Pulmonary Inflammation in Cystic Fibrosis

Becker

Riethmüller²,

Zhang³

et al. 2010

TORMJ

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Sphingolipids and in particular ceramide have been shown to be critically involved in the response to many receptor-mediated, but also receptor-independent, mainly stress stimuli. Recent studies demonstrate that ceramide plays an important role in the pathogenesis of cystic fibrosis, a hereditary metabolic disorder caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator. Patients with cystic fibrosis suffer from chronic pulmonary inflammation and microbial lung infections, in particular with Pseudomonas aeruginosa. Chronic pulmonary inflammation in these patients seems to be the initial pathophysiological event. Inflammation may finally result in the high infection susceptibility of these patients, fibrosis and loss of lung function. Recent studies demonstrated that ceramide accumulates in lungs of cystic fibrosis mice and causes age-dependent pulmonary inflammation as indicated by accumulation of neutrophils and macrophages in the lung and increased pulmonary concentrations of Interleukins 1 and 8, death of bronchial epithelial cells, deposition of DNA in bronchi and high susceptibility to Pseudomonas aeruginosa infections. Genetic or pharmacological inhibition of the acid sphingomyelinase blocks excessive ceramide production in lungs of cystic fibrosis mice and corrects pathological lung findings. First clinical studies confirm that inhibition of the acid sphingomyelinase with small molecules might be a novel strategy to treat patients with cystic fibrosis.

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“…The sphingoid backbone is an aliphatic 2-amino-1,3-diol. From this basic lipid, addition of fatty acids that are typicallyBriefly, sphingolipids are synthesized de novo from serine and palmitate, which condense serine and palmitoyl CoA to form 3-keto-dihydrosphingosine through the action of serine palmitoyltransferase (SPT) [15][16][17]. This is then reduced to produce dihydrosphingosine (sphinganine), which is then acylated by dihydroceramide synthases (also known CerS) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer

Yandım

Apohan

Baran

2012

Cancer Chemother Pharmacol

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Sphingolipids including ceramides and its derivatives such as ceramide-1-phosphate, glucosylceramide (GlcCer), and sphingosine-1-phosphate are essential structural components of cell membranes. They now recognized as novel bioeffector molecules which control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramide, the central molecule of sphingolipid metabolism, generally mediates anti-proliferative responses such as inhibition of cell growth, induction of apoptosis, and/or modulation of senescence. There are two major classes of sphingolipids. One of them is glycosphingolipids which are synthesized from the hydrophobic molecule, ceramide. GlcCer, generated by glucosylceramide synthase (GCS) that transfers the glucose from UDPglucose to ceramide, is an important glycosphingolipid metabolic intermediate. GCS regulates the balance between apoptotic ceramide and antiapoptotic GlcCer. Downregulation or inhibition of GCS results in increased apoptosis and decreased drug resistance. The mechanism underlying the drug resistance which develops with increased glucosylceramide expression is associated with P-glycoprotein. In various types of cancers, overexpression of GCS has been observed which renders GCS a good target for the treatment of cancer. This review summarizes our current knowledge on the structure and functions of glucosylceramide synthase and glucosylceramide and on the roles of glucosylceramide synthase in cancer therapy and drug resistance.

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Principles of bioactive lipid signalling: lessons from sphingolipids

Cited by 2,927 publications

References 117 publications

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

The Role of Sphingolipids and Ceramide in Pulmonary Inflammation in Cystic Fibrosis

Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer

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