Amyloid‐β peptide enhances tumor necrosis factor‐α‐induced iNOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes

Zeng, Chenbo; Lee, J. T.; Chen, H.; Chen, S.; Hsu, Chung Y.; Xu, Jianlong

doi:10.1111/j.1471-4159.2005.03217.x

Cited by 62 publications

(56 citation statements)

References 53 publications

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“…Two forms of Aβ are generally used for in vitro studies, fibrillar and oligomer. Several studies suggest that fibrillar Aβ induces primary neuron apoptosis via the activation of NSM (Ayasolla et al, 2004;Chen et al, 2006;Jana and Pahan, 2004;Lee et al, 2004;Satoi et al, 2005;Zeng et al, 2005). However, our data using postmortem AD brain revealed that ASM, not NSM, activity was elevated.…”

Section: Discussioncontrasting

confidence: 80%

“…In vitro, Aβ has been shown to induce apoptosis via the sphingomyelin/ceramide pathway in various brain cells, including human and rat primary neurons (Jana and Pahan, 2004;Ju et al, 2005;Malaplate-Armand et al, 2006), rat oligodendrocytes (Cheng et al, 2003;Lee et al, 2004;Malaplate-Armand et al, 2006;Zeng et al, 2005), rat astrocytes and glial cells (Ayasolla et al, 2004), and murine neuroblastoma cells (Satoi et al, 2005). Calcium-dependent phospholipase A (cPLA) (Malaplate-Armand et al, 2006), inducible nitric oxide synthase (iNOS) (Ayasolla et al, 2004;Zeng et al, 2005), the p75 neurotrophin receptor (p75NTR) (Costantini et al, 2005), and NADPH oxidase (Jana and Pahan, 2004) have each been shown to be involved in the Aβ-related activation of the sphingomyelin/ceramide pathway. Tumor necrosis factor-alpha (TNF-α) (Ayasolla et al, 2004;Zeng et al, 2005) and interleukin-6 (Fiebich et al, 1995) also are involved in Aβ-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…Calcium-dependent phospholipase A (cPLA) (Malaplate-Armand et al, 2006), inducible nitric oxide synthase (iNOS) (Ayasolla et al, 2004;Zeng et al, 2005), the p75 neurotrophin receptor (p75NTR) (Costantini et al, 2005), and NADPH oxidase (Jana and Pahan, 2004) have each been shown to be involved in the Aβ-related activation of the sphingomyelin/ceramide pathway. Tumor necrosis factor-alpha (TNF-α) (Ayasolla et al, 2004;Zeng et al, 2005) and interleukin-6 (Fiebich et al, 1995) also are involved in Aβ-induced apoptosis. In vivo, Alessenko and colleagues found that the activation of the sphingomyelin/ceramide pathway lies downstream of the oxidative stress that follows Aβ administration (Alessenko et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Deregulation of sphingolipid metabolism in Alzheimer's disease

Huang²,

Li³

et al. 2010

Neurobiology of Aging

442

468

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Abnormal sphingolipid metabolism has been previously reported in Alzheimer's disease (AD). To extend these findings, several sphingolipids and sphingolipid hydrolases were analyzed in brain samples from AD patients and age-matched normal individuals. We found a pattern of elevated acid sphingomyelinase (ASM) and acid ceramidase (AC) expression in AD, leading to a reduction in sphingomyelin and elevation of ceramide. More sphingosine also was found in the AD brains, although sphingosine-1-phosphate (S1P) levels were reduced. Notably, significant correlations were observed between the brain ASM and S1P levels and the levels of amyloid beta peptide (Aβ) and phosphorylated tau protein. Based on these findings, neuronal cell cultures were treated with Aβ oligomers, which were found to activate ASM, increase ceramide, and induce apoptosis. Pretreatment of the neurons with purified, recombinant AC prevented the cells from undergoing Aβ-induced apoptosis. We propose that ASM activation is an important pathological event leading to AD, perhaps due to Aβ deposition. The downstream consequences of ASM activation are elevated ceramide, activation of ceramidases, and production of sphingosine. The reduced levels of S1P in the AD brain, together with elevated ceramide, likely contribute to the disease pathogenesis.

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Section: Discussioncontrasting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Deregulation of sphingolipid metabolism in Alzheimer's disease

Huang²,

Li³

et al. 2010

Neurobiology of Aging

442

468

View full text Add to dashboard Cite

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“…However, in vivo, where contributing factors relating to microglia-derived reactive oxygen species and cytokines, such as tumor necrosis factor-␣ (TNF-␣) are present, the selective impact on mature myelinating oligodendrocytes could be greater. In fact, Zeng and colleagues have shown that A␤ enhances TNF-␣-mediated oligodendrocyte demise through a sphingomyelinase/ceramide pathway, 43 while our laboratory has previously reported enhanced levels of TNF-␣ within the brains of 3ϫTg-AD mice at ages identical to when oligodendrocyte/myelin deficits become evident.…”

Section: Discussionmentioning

confidence: 99%

Early Oligodendrocyte/Myelin Pathology in Alzheimer's Disease Mice Constitutes a Novel Therapeutic Target

Desai

Mastrangelo

Ryan

et al. 2010

The American Journal of Pathology

183

173

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The detection of myelin disruptions in Alzheimer's disease (AD)-affected brain raises the possibility that oligodendrocytes undergo pathophysiological assault over the protracted course of this neurodegenerative disease. Oligodendrocyte compromise arising from direct toxic effects imparted by pathological amyloid-␤ peptides and/or through signals derived from degenerating neurons could play an important role in the disease process. We previously demonstrated that 3؋Tg-AD mice, which harbor the human amyloid precursor protein Swedish mutant transgene, presenilin knock-in mutation, and tau P301L mutant transgene, exhibit significant alterations in overall myelination patterns and oligodendrocyte status at time points preceding the appearance of amyloid and tau pathology. Herein, we demonstrate that A␤ 1-42 leads to increased caspase-3 expression and apoptotic cell death of both nondifferentiated and differentiated mouse oligodendrocyte precursor (mOP) cells in vitro. Through use of a recombinant adeno-associated virus serotype-2 (rAAV2) vector expressing an A␤ 1-42 -specific intracellular antibody (intrabody), oligodendrocyte and myelin marker expression, as well as myelin integrity, were restored in the vector-infused brain regions of 3؋Tg-AD mice. Overall, this work provides further insights into the impact of A␤ 1-42 -mediated toxicity on the temporal and spatial progression of subtle myelin disruption during the early presymptomatic stages of AD and may help to validate new therapeutic options designed to avert these early impairments.

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“…120 Ab also indirectly contributes to oxidative stress by upregulating inducible nitric oxide synthase (iNOS) in mature OLs through a TNF-a-mediated ceramide pathway. 121 Finally, injection of Ab into the corpus callosum of rats induced myelin damage and OL apoptosis. In this experiment, activated microglia were also seen, 122 further implicating pro-inflammatory molecules such as TNF-a.…”

Section: Ols and Diseasementioning

confidence: 99%

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

2008

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Apoptosis plays a crucial role in brain development by ensuring that only appropriately growing, migrating, and synapse-forming neurons and their associated glial cells survive. This process involves an intimate relationship between cell-cell interactions and developmental cues and is further impacted by environmental stress during neurogenesis and disease. Oligodendrocytes (OLs), the major myelin-forming cells in the central nervous system, largely form after this wave of neurogenesis but also show a selective vulnerability to cell death stimuli depending on their stage of development. This can affect not only embryonic and early postnatal brain formation but also the response to demyelinating pathologies. In the present review, we discuss the stagespecific sensitivity of OL lineage cells to damage-induced death and how this might impact myelin survival and regeneration during injury or disease. Apoptosis is a major form of programmed cell death required for the normal development of metazoan tissues, including the brain. 1 During embryonic development of the brain, many more cells than ultimately needed are generated and then selection occurs, resulting in the apoptotic depletion of the surplus cells. The importance of the apoptotic pathway in early brain development has been demonstrated by the targeted deletion in mice of the death-specific cysteine proteases caspase-3 or caspase-9, or of the co-activator Apaf-1, all of which cause severe brain overgrowth and perinatal death. 2,3 In the adult brain, 90% of the cells belong to the glial lineage, which includes oligodendrocytes (OLs), astrocytes and microglia. The glia ensures proper development, function and repair of the neuronal network. This is possible through continuous cross-talk between the glia and neurons mediated by neurotransmitters, cytokines, growth and trophic factor secretion and signaling in a reciprocal manner. [4][5][6][7] In the central nervous system (CNS), OLs are responsible for axon myelination, which insulates the electrical signals transmitted between neurons. OL and neuron development is tightly regulated and the myelin sheath is constructed only when OLs reach maturity and neurons have grown appropriately. In response to injury or during the course of neurological diseases, the neuron-glia network can be replenished to some extent but the degree of repair is dependent on the developmental stage of the OL. This complexity is compounded by the differential sensitivity of OL lineage cells to apoptotic stimuli. In the present review, we will first briefly examine the stages of differentiation of OL cells and then discuss several diseases that are impacted by OL apoptosis, noting how the stage of cell differentiation governs the sensitivity to apoptosis. Defined Stages of OL DevelopmentOligodendrocyte development can be divided into four distinct stages according to the temporal expression of cell surface markers and morphology (Table 1). 8 In the first stage, OL progenitor cells (OPCs) originate from the neuroepithelium of the ventricul...

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Amyloid‐β peptide enhances tumor necrosis factor‐α‐induced iNOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes

Cited by 62 publications

References 53 publications

Deregulation of sphingolipid metabolism in Alzheimer's disease

Deregulation of sphingolipid metabolism in Alzheimer's disease

Early Oligodendrocyte/Myelin Pathology in Alzheimer's Disease Mice Constitutes a Novel Therapeutic Target

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

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