Activation of LA‐N‐2 cell phospholipases by single alanine substitution analogs of amyloid β peptide (25–35)

Singh, Indrapal N.; Sato, Kazuki; Takashima, Akihiko; Kanfer, Julian N.

doi:10.1016/s0014-5793(97)00154-3

Cited by 12 publications

(4 citation statements)

References 14 publications

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“…The lack of cPLA 2 immunoreactivity in the PDAPP was unexpected, given our results in the AD cortex and the observation that an amyloid fragment itself, when applied exogenously to cultured cells, can induce cPLA 2 activity (Singh et al, 1997). However, our results in AD brain showed that amyloid alone did not directly account for cPLA 2 increases, as cPLA 2 immunoreactivity was not observed in the cerebellum of AD cases studied, despite the presence in this region of diffuse amyloid and amyloid angiopathy.…”

Section: Discussionmentioning

confidence: 70%

Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration

Stephenson

Rash

Smalstig

et al. 1999

Glia

142

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Section: Discussionmentioning

confidence: 70%

Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration

Stephenson

Rash

Smalstig

et al. 1999

Glia

142

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“…Previous studies have implicated PLD in AD pathogenesis either as a mediator of APP trafficking, presenilin regulation or downstream target of Aβ (Kanfer et al, 1986; Kanfer et al, 1996; Singh et al, 1997a; Singh et al, 1997b; Kanfer et al, 1998; Singh et al, 1998; Cai et al, 2006a; Cai et al, 2006b; Jin et al, 2007; Brandenburg et al, 2008; Liu et al, 2009; Oliveira and Di Paolo, 2010). Importantly, an increase in total PLD activity was reported in AD brain homogenates, using an in vitro enzymatic assay (Kanfer et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Phospholipase D2 Ablation Ameliorates Alzheimer's Disease-Linked Synaptic Dysfunction and Cognitive Deficits

Oliveira¹,

Chan²,

Huang³

et al. 2010

J. Neurosci.

161

168

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Growing evidence implicates aberrant lipid signaling in Alzheimer's disease (AD). While phospholipases A2 and C have been recentlyshown to mediate key actions of amyloid ␤-peptide (A␤) through a dysregulation of arachidonic acid and phosphatidylinositol-4,5-bisphosphate metabolism, respectively, the role of phospholipase D (PLD) has so far remained elusive. PLD produces phosphatidic acid (PA), a bioactive lipid involved in multiple aspects of cell physiology, including signaling and membrane trafficking processes. Here we show that oligomeric A␤ enhances PLD activity in cultured neurons and that this stimulatory effect does not occur upon ablation of PLD2 via gene targeting. A␤ fails to suppress long-term potentiation in PLD2-deficient hippocampal slices, suggesting that PLD2 is required for the synaptotoxic action of this peptide. In vivo PLD activity, as assessed by detection of phosphatidylethanol levels using mass spectrometry (MS) following ethanol injection, is also increased in the brain of a transgenic mouse model of AD (SwAPP). Furthermore, Pld2 ablation rescues memory deficits and confers synaptic protection in SwAPP mice despite a significant A␤ load. MS-based lipid analysis of Pld2 mutant brains in the presence or absence of the SwAPP transgene unmasks striking crosstalks between different PA species. This lipid analysis shows an exquisite acyl chain specificity and plasticity in the perturbation of PA metabolism. Collectively, our results point to specific molecular species of PA as key modulators of AD pathogenesis and identify PLD2 as a novel potential target for therapeutics.

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“…Additionally, the same group showed that indomethacin (a non-steroid anti-inflammatory drug), nordihydroguaiaretic acid (an anti-oxidant drug) and nicotine inhibited the increase in PLD activity produced by Aβ25-35 applications [69, 70]. Furthermore, alanine substitution for the amino acids on the position 29-34 of Aβ25-35 prevented the peptide from having an effect on PLD activity [71]. Finally, pre-treatment with Aβ25-35 desensitized the cells, which did not exhibit a PLD activity increase in response to a new Aβ25-35 treatment, thus prompting the authors to suggest that Aβ25-35 might mediate its effects on PLD upon receptor binding [70].…”

Section: Links Between Pld and Alzheimer’s Diseasementioning

confidence: 99%

Phospholipase D in brain function and Alzheimer's disease

Oliveira

Paolo

2010

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Alzheimer’s disease is the most common neurodegenerative disorder. Although lipids are major constituents of brain, their role in Alzheimer’s disease pathogenesis is poorly understood. Much attention has been given to cholesterol, but growing evidence suggests that other lipids, such as phospholipids, might play an important role in this disorder. In this review, we will summarize the evidence linking phospholipase D, a phosphatidic acid-synthesizing enzyme, to multiple aspects of normal brain function and to Alzheimer’s disease. The role of phospholipase D in signaling mechanisms downstream of beta-amyloid as well as in the trafficking and processing of amyloid precursor protein will be emphasized.

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Activation of LA‐N‐2 cell phospholipases by single alanine substitution analogs of amyloid β peptide (25–35)

Cited by 12 publications

References 14 publications

Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration

Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration

Phospholipase D2 Ablation Ameliorates Alzheimer's Disease-Linked Synaptic Dysfunction and Cognitive Deficits

Phospholipase D in brain function and Alzheimer's disease

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