Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain

Velasco‐Estevez, María; O’Sullivan, Catherine; Sheridan, Graham K.

doi:10.1016/j.neuropharm.2016.04.002

Cited by 67 publications

(48 citation statements)

References 111 publications

(104 reference statements)

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“…5). A similar pattern of PC breakdown and enhanced LPA signaling was evidenced in other neurological diseases, such as schizophrenia, and proposed to be involved in demyelination processes (64,65). In the dHC, an increase of PL levels occurs, despite increased cPLA 2 expression, indicating that PL metabolism in the dHC is not solely regulated by cPLA 2 , and that increased cPLA 2 expression is implicated in an alternative pathway.…”

Section: Discussionsupporting

confidence: 58%

Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls

Lerner

Post

Ellis

et al. 2018

Journal of Lipid Research

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In this study, we report the development of a dual extraction protocol for RNA and lipids, including phospholipids, endocannabinoids, and arachidonic acid, at high spatial resolution, e.g., brain punches obtained from whole frozen brains corresponding to four brain subregions: dorsal hippocampus, ventral hippocampus, basolateral amygdala, and hypothalamus. This extraction method combined with LC/multiple reaction monitoring for lipid quantifi-cation and quantitative PCR for RNA investigation allows lipidomic and transcriptomic profiling from submilligram amounts of tissue, thus benefiting the time and animal costs for analysis and the data reliability due to prevention of biological variability between animal batches and/or tissue heterogeneity, as compared with profiling in distinct animal batches. Moreover, the method allows a higher extraction efficiency and integrity preservation for RNA, while allowing concurrently quantitative analysis of low and high abundant lipids. The method was applied for brain punches obtained 1 h after kainic acid-induced epileptic seizures in mice (n = 10) compared with controls (n = 10), and enabled the provision of valuable new insights into the subregional lipid and RNA changes with epilepsy, highlighting its potential as a new viable tool in quantitative neurobiology.

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Section: Discussionsupporting

confidence: 58%

Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls

Lerner

Post

Ellis

et al. 2018

Journal of Lipid Research

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show abstract

“…This bioactive and proinflammatory lysophospholipid is highly produced during inflammation and activates microglial cells which, in turn, self-sustains LPA synthesis4647. Beyond acting on its high-affinity metabotropic receptors LPA1 – 4, LPA also binds to the TRPV1 C-terminal48.…”

Section: Resultsmentioning

confidence: 99%

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

et al. 2017

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The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.

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“…This indicates that LPA 5 signaling is related to neuropathic pain mediated by multiple sclerosis [96]. It was found that intravenous LPA and GGPP (LPA 5 agonists) induced allodynia, but GGPP-induced allodynia did not show up in LPA 5 -KO mice, indicating pain signals in the spinal cord by LPA 5 transfer [94][95][96].…”

Section: Lpar and Neuropathic Painmentioning

confidence: 99%

“…LPA may activate macrophages/microglia via LPAR1 and LPAR3 and promote self-amplification of LPA, increasing microglial migration and pro-inflammatory phenotype through the LPAR5/protein kinase D (PKD) axis. Activation and migration of microglia are associated with demyelination in the spinal cord after injury, and microglia are more involved in the initiation of neuropathic pain (NP) [94,95]. In the cuprizone (CPZ)-induced multiple sclerosis (MS) model, LPA5 signaling mediates pain allergy induced by A-delta fibers and demyelination produced by CPZ.…”

Section: Lpar and Neuropathic Painmentioning

confidence: 99%

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

Xiang¹,

Lü²,

Shao³

et al. 2020

J. Cancer

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Lysophosphatidic acid (LPA, 1-acyl-2-hemolytic-sn-glycerol-3-phosphate) extracted from membrane phospholipid is a kind of simple bioactive glycophospholipid, which has many biological functions such as stimulating cell multiplication, cytoskeleton recombination, cell survival, drug-fast, synthesis of DNA and ion transport. Current studies have shown that six G-coupled protein receptors (LPAR1-6) can be activated by LPA. They stimulate a variety of signal transduction pathways through heterotrimeric G-proteins (such as Gα12/13, Gαq/11, Gαi/o and GαS). LPA and its receptors play vital roles in cancers, nervous system diseases, cardiovascular diseases, liver diseases, metabolic diseases, etc. In this article, we discussed the structure of LPA receptors and elucidated their functions in various diseases, in order to better understand them and point out new therapeutic schemes for them.

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Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain

Cited by 67 publications

References 111 publications

Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls

Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

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