Sphingolipid-Enriched Extracellular Vesicles and Alzheimer’s Disease: A Decade of Research

Dinkins, Michael B.; Wang, Guanghu; Bieberich, Erhard

doi:10.3233/jad-160567

Cited by 61 publications

(64 citation statements)

References 108 publications

(159 reference statements)

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“…Quantification of complex lipids in human milk shows that sphingomyelin is the most abundant, making up about 36% of complex lipids, followed by glycerophospholipids, phosphatidylethanolamine (29%), and phosphatidylcholine (25%) [23,32,33]. Exosomes are also enriched with sphingolipids, particularly ceramide and sphingomyelin, and glycerophospholipids such as phosphatidylserine [34]. Like fatty acid levels, the composition of sphingolipids in breast milk can also be modified by diet.…”

Section: Complex Lipids In Breast Milkmentioning

confidence: 99%

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

et al. 2020

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Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.

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Section: Complex Lipids In Breast Milkmentioning

confidence: 99%

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

et al. 2020

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“…Wang et al, 2012). To date, inhibition or genetic deficiency of nSMase2 is a method widely used to prevent exosome secretion in various cell types and tissues (Chairoungdua, Smith, Pochard, Hull, & Caplan, 2010; Dinkins et al, 2014; Dinkins, Enasko, et al, 2016; Dinkins, Wang, & Bieberich, 2016; Goldkorn, Chung, & Filosto, 2013; Guo, Bellingham, & Hill, 2015; Kong, He, et al, 2015; Kosaka et al, 2010; Marsh & van Meer, 2008; Menck et al, 2017; Shamseddine, Airola, & Hannun, 2015; Tan et al, 2013; Trajkovic et al, 2008; Yuyama, Sun, Mitsutake, & Igarashi, 2012). nSMase2 converts sphingomyelin into ceramide, a reaction shown to be instrumental for exosome secretion in vitro (Trajkovic et al, 2008) (Fig.…”

Section: Got Exosomes: What’s (Really) In Your Prep?mentioning

confidence: 99%

“…1A). Our laboratory showed that inhibition and genetic deficiency of nSMase2 also suppresses exosome secretion in vivo (Dinkins et al, 2014; Dinkins, Enasko, et al, 2016; Dinkins, Wang, et al, 2016). These discoveries and the critical role of ceramide for the function of exosomes, particularly in cancer, will be discussed in the next sections of this review.…”

Section: Got Exosomes: What’s (Really) In Your Prep?mentioning

confidence: 99%

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Elsherbini

Bieberich

2018

Advances in Cancer Research

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114

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Exosomes are secreted extracellular vesicles (EVs) that carry micro RNAs and other factors to reprogram cancer cells and tissues affected by cancer. Exosomes are exchanged between cancer cells and other tissues, often to prepare a premetastatic niche, escape immune surveillance, or spread multidrug resistance. Only a few studies investigated the function of lipids in exosomes, although their lipid composition is different from that of the secreting cells. Ceramide is one of the lipids critical for exosome formation and it is also enriched in these EVs. New research suggests that lipids in the exosomal membrane may organize and transmit “mobile rafts” that turn exosomes into extracellular signalosomes spreading activation of cell signaling pathways in oncogenesis and metastasis. Ceramide may modulate the function of mobile rafts and their effect on these cell signaling pathways. The critical role of lipids and in particular, ceramide for formation, secretion, and function of exosomes may lead to a radically new understanding of cancer biology and therapy.

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“…The process by which Aβ binds to exosomes is complex. Glycosphingolipids (GSLs), which are involved in exosome release mechanisms, bind to cytosolic Aβ and are present both in the cell membrane and in exosomes (Dinkins, Wang, & Bieberich, 2017). Degradation of GSL-glycans with endoglycoceramidase (EGCase) prevent the association between Aβ and exosomes (Yuyama et al, 2015;Yuyama & Igarashi, 2017).…”

Section: Exosome Cargo In Ad and Ds-admentioning

confidence: 99%

Exosome release and cargo in Down syndrome

Hamlett

LaRosa

Mufson

et al. 2019

Developmental Neurobiology

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Down syndrome (DS) is a multisystem disorder affecting 1 in 800 births worldwide. Advancing technology, medical treatment, and social intervention have dramatically increased life expectancy, yet there are many etiologies of this disorder that are in need of further research. The advent of the ability to capture extracellular vesicles (EVs) in blood from specific cell types allows for the investigation of novel intracellular processes. Exosomes are one type of EVs that have demonstrated great potential in uncovering new biomarkers of neurodegeneration and disease, and also that appear to be intricately involved in the transsynaptic spread of pathogenic factors underlying Alzheimer's disease and other neurological diseases. Exosomes are nanosized vesicles, generated in endosomal multivesicular bodies (MVBs) and secreted by most cells in the body. Since exosomes are important mediators of intercellular communication and genetic exchange, they have emerged as a major research focus and have revealed novel biological sequelae involved in conditions afflicting the DS population. This review summarizes current knowledge on exosome biology in individuals with DS, both early in life and in aging individuals. Collectively these studies have demonstrated that complex multicellular processes underlying DS etiologies may include abnormal formation and secretion of extracellular vesicles such as exosomes.

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Sphingolipid-Enriched Extracellular Vesicles and Alzheimer’s Disease: A Decade of Research

Cited by 61 publications

References 108 publications

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Exosome release and cargo in Down syndrome

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