Role of Cytosolic Calcium-Dependent Phospholipase A2 in Alzheimer's Disease Pathogenesis

Gentile, Maria Teresa; Reccia, Mafalda Giovanna; Sorrentino, Pierpaolo; Vitale, Emilia; Sorrentino, Giuseppe; Puca, Annibale Alessandro; Colucci-D’Amato, Luca

doi:10.1007/s12035-012-8279-4

Cited by 49 publications

(40 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…RASGRP3 is a calcium and DAG-regulated RAS guanyl releasing protein which can activate small GTPases such as RAS and RAP1 [25]. PLA2G4A is a member of phospholipases A2 (PLA2s) superfamily, which regulates the release of arachidonic acid (AA) [26]. Although calmodulin is also a family of Ca 2+ binding proteins and mediates many important cellular processes [27], CALM2 (calmodulin 2) gene was downregulated.…”

Section: Resultsmentioning

confidence: 99%

Substrate-dependent gene regulation of self-assembled human MSC spheroids on chitosan membranes

Yeh

Liu

Sieber³

et al. 2014

BMC Genomics

View full text Add to dashboard Cite

BackgroundThree-dimensional (3D) multicellular spheroids of mesenchymal stem cells (MSCs) are generally regarded to have beneficial properties over MSCs in monolayer. Recent literatures have documented that MSCs can self-assemble into 3D spheroids with a greater capacity for differentiation into various cell types when grown on chitosan (CS), a biopolymer. The genomic modulation occurring in these MSC spheroids is thus of essential importance for understanding their uniqueness and therapeutic potentials. In this study, 3D spheroids self-assembled from human umbilical cord MSCs grown on CS membranes were analyzed by mRNA as well as microRNA microarrays, which helped identify the critical signaling events that may alter the cellular functions during the spheroid forming process.ResultsGenes screened from mRNA and microRNA cross-correlation analyses were further confirmed with the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. Results revealed the regulation of a significant number of calcium-associated genes, which suggested the crucial role of calcium signaling in CS-derived MSC spheroids. In addition, many genes associated with the multilineage differentiation capacities and those associated with the antiinflammatory and antitumor properties of MSCs were upregulated. The genetic modulation was significantly more remarkable and endured longer for MSC spheroids derived on CS substrates compared to those derived on a non-adherent (polyvinyl alcohol) substrate.ConclusionsBased on the study, the culture substrates used to prepare 3D MSC spheroids may predefine their properties through cell-substrate interaction.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-10) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Substrate-dependent gene regulation of self-assembled human MSC spheroids on chitosan membranes

Yeh

Liu

Sieber³

et al. 2014

BMC Genomics

View full text Add to dashboard Cite

show abstract

“…In brain, cPLA 2 has been shown to co-localize with glial fibrillary acidic protein (GFAP), a principal marker for brain astrocytes [113]. Moreover, under brain inflammatory and neurodegenerative conditions such as AD, there is an increase in immunoreactivity to cPLA 2 in astrocytes from the cortex of patients [114, 115]. A variety of proinflammatory factors including IL-1 β , TNF- α , or BK may exert as modulators of cPLA 2 activity and/or expression in various cell types including astrocytes [23, 111].…”

Section: Role Of Redox Signaling In the Regulation Of Inflammatorymentioning

confidence: 99%

Role of Redox Signaling in Neuroinflammation and Neurodegenerative Diseases

Hsieh

Yang

2013

BioMed Research International

300

281

View full text Add to dashboard Cite

Reactive oxygen species (ROS), a redox signal, are produced by various enzymatic reactions and chemical processes, which are essential for many physiological functions and act as second messengers. However, accumulating evidence has implicated the pathogenesis of several human diseases including neurodegenerative disorders related to increased oxidative stress. Under pathological conditions, increasing ROS production can regulate the expression of diverse inflammatory mediators during brain injury. Elevated levels of several proinflammatory factors including cytokines, peptides, pathogenic structures, and peroxidants in the central nervous system (CNS) have been detected in patients with neurodegenerative diseases such as Alzheimer's disease (AD). These proinflammatory factors act as potent stimuli in brain inflammation through upregulation of diverse inflammatory genes, including matrix metalloproteinases (MMPs), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and adhesion molecules. To date, the intracellular signaling mechanisms underlying the expression of target proteins regulated by these factors are elusive. In this review, we discuss the mechanisms underlying the intracellular signaling pathways, especially ROS, involved in the expression of several inflammatory proteins induced by proinflammatory factors in brain resident cells. Understanding redox signaling transduction mechanisms involved in the expression of target proteins and genes may provide useful therapeutic strategies for brain injury, inflammation, and neurodegenerative diseases.

show abstract

“…The role of calcium-dependent phospholipase A2 in phospholipid breakdown was investigated a long time ago [ 23 , 24 ]. However, the cytosolic effect of different isoenzymes (isoforms) of PLA2 on AD was only recently reviewed [ 25 ]. Amyloid peptide increases choline conductance and choline fluxes in PCl2 cells.…”

Section: Potential Role Of Choline In Ad or Neurodegenerationmentioning

confidence: 99%

Choline-containing phospholipids: relevance to brain functional pathways

Tayebati

Amenta

2013

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Choline participates in several relevant neurochemical processes. It is the precursor and metabolite of acetylcholine (ACh), plays a role in single-carbon metabolism and is an essential component of different membrane phospholipids (PLs). PLs are structural components of cell membranes involved in intraneuronal signal transduction. This paper reviews the roles of choline and of choline-containing phospholipids (CCPLs) on brain metabolism in health and disease followed by an analysis of the effects of exogenously administered CCPLs on the brain, a topic extensively investigated by literature. Based on the observation of decreased cholinergic neurotransmission in brain disorders characterized by cognitive impairment, cholinergic precursor loading therapy with CCPLs was the first approach used to attempt for relieving the cognitive symptoms of Alzheimer ' s disease. This therapeutic strategy was discontinued due to the negative clinical results obtained with choline or lecithin. Negative results obtained with some compounds cannot be generalized for all CCPLs, as CDP-choline (citicoline) and to a greater extent choline alphoscerate (GPC) displayed interesting effects documented in preclinical studies and limited clinical trials. We provide evidence in favor of CDP-choline and GPC activity in cerebrovascular or neurodegenerative disorders characterized by cholinergic neurotransmission impairment. Based on the results of the controlled clinical trials available, we suggest that due to the lack of novel therapeutic strategies, safe compounds developed a long time ago such as effective CCPLs could have still a place in pharmacotherapy. Therefore selected compounds of this class should be further investigated by new appropriate clinical studies.

show abstract

Role of Cytosolic Calcium-Dependent Phospholipase A2 in Alzheimer's Disease Pathogenesis

Cited by 49 publications

References 76 publications

Substrate-dependent gene regulation of self-assembled human MSC spheroids on chitosan membranes

Substrate-dependent gene regulation of self-assembled human MSC spheroids on chitosan membranes

Role of Redox Signaling in Neuroinflammation and Neurodegenerative Diseases

Choline-containing phospholipids: relevance to brain functional pathways

Contact Info

Product

Resources

About