Sphingolipids: Critical players in Alzheimer’s disease

Echten‐Deckert, Gerhild van; Walter, Jochen

doi:10.1016/j.plipres.2012.07.001

Cited by 152 publications

(124 citation statements)

References 272 publications

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“…Materials-APAP, acetaminophen sulfate, acetaminophen glucuronide, D-galactosamine, CCl 4 , TAA, fumonisin B1 (FB1), MK571, chloroquine, and L-buthionine sulfoximine were from Sigma-Aldrich. Acetaminophen-glutathione (APAP-GSH) was from Santa Cruz Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

“…Surprisingly, CerS2 null mice were largely resistant to the hepatotoxic effects of APAP, D-galactosamine, CCl 4 , and thioacetamide (TAA), mainly because of altered gap junction function as a result of mislocalization of connexin (Cx) 32, a key player in gap junctions. We suggest that the SL pathway might be a novel drug target for alleviating drug-induced liver damage and possibly other forms of acute liver failure.…”

mentioning

confidence: 99%

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Protection of a Ceramide Synthase 2 Null Mouse from Drug-induced Liver Injury

Park

Erez-Roman

et al. 2013

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Protection of a Ceramide Synthase 2 Null Mouse from Drug-induced Liver Injury

Park

Erez-Roman

et al. 2013

Journal of Biological Chemistry

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“…Among these alterations, abnormal sphingolipid metabolism has been reported in AD tissues (van Echten‐Deckert & Walter, 2012). Specifically, there is an upregulation of de novo ceramide synthesis (Grimm et al , 2011) and an increase in the activity of sphingomyelinase (SMase), which catabolizes sphingomyelin (SM) into ceramide (Filippov et al , 2012).…”

Section: Introductionmentioning

confidence: 99%

Increased localization of APP‐C99 in mitochondria‐associated ER membranes causes mitochondrial dysfunction in Alzheimer disease

et al. 2017

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In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by β‐secretase to generate a 99‐aa C‐terminal fragment (C99) that is then cleaved by γ‐secretase to generate the β‐amyloid (Aβ) found in senile plaques. In previous reports, we and others have shown that γ‐secretase activity is enriched in mitochondria‐associated endoplasmic reticulum (ER) membranes (MAM) and that ER–mitochondrial connectivity and MAM function are upregulated in AD. We now show that C99, in addition to its localization in endosomes, can also be found in MAM, where it is normally processed rapidly by γ‐secretase. In cell models of AD, however, the concentration of unprocessed C99 increases in MAM regions, resulting in elevated sphingolipid turnover and an altered lipid composition of both MAM and mitochondrial membranes. In turn, this change in mitochondrial membrane composition interferes with the proper assembly and activity of mitochondrial respiratory supercomplexes, thereby likely contributing to the bioenergetic defects characteristic of AD.

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“…Gangliosides play an important role in the development and physiology of the brain (11). As compared with astrocytes and oligodendrocytes, postmitotic neurons express particularly high levels of complex gangliosides (12). Gangliosides can serve as interaction molecules for surface proteins, e.g.…”

mentioning

confidence: 99%

Ablation of Neuronal Ceramide Synthase 1 in Mice Decreases Ganglioside Levels and Expression of Myelin-associated Glycoprotein in Oligodendrocytes

Ginkel

Hartmann

Dorp

et al. 2012

Journal of Biological Chemistry

124

114

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Background: Ceramide synthase 1 catalyzes the synthesis of C18 ceramide and is mainly expressed in neurons of the brain. Results: Ablation of ceramide synthase 1 decreases ganglioside levels and expression of oligodendrocytic myelin-associated glycoprotein in motor-impaired mice. Conclusion: CerS1-derived C18 gangliosides are essential for cerebellar development and neurodevelopmentally regulated behavior in mice. Significance: Neuronal gangliosides regulate expression of myelin-associated glycoprotein in oligodendrocytes.

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Sphingolipids: Critical players in Alzheimer’s disease

Cited by 152 publications

References 272 publications

Protection of a Ceramide Synthase 2 Null Mouse from Drug-induced Liver Injury

Protection of a Ceramide Synthase 2 Null Mouse from Drug-induced Liver Injury

Increased localization of APP‐C99 in mitochondria‐associated ER membranes causes mitochondrial dysfunction in Alzheimer disease

Ablation of Neuronal Ceramide Synthase 1 in Mice Decreases Ganglioside Levels and Expression of Myelin-associated Glycoprotein in Oligodendrocytes

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