Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases

Herr, Deron R.; Chew, Wee; Satish, Ramapatna L.; Ong, Wei‐Yi

doi:10.1007/s12035-019-01719-1

Cited by 38 publications

(50 citation statements)

References 186 publications

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“…The LPA deregulation has been studied in complex disorder such as schizophrenia in preclinical models 31,51 and schizophrenia patients 52 . Finally, ATX as the primary biological source of LPA, represents a high-value psychiatric condition target 53 . ATX has been described as a possible biomarker of patients with major depression disorder diagnosis, since the serum levels of this enzyme are reduced in depressive patients compared with healthy controls 54 .…”

Section: Discussionmentioning

confidence: 99%

Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

García-Marchena

Pizarro

Pavón

et al. 2020

Sci Rep

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Lysophosphatidic acid (LPA) species are bioactive lipids participating in neurodevelopmental processes. The aim was to investigate whether the relevant species of LPA were associated with clinical features of alcohol addiction. A total of 55 abstinent alcohol use disorder (AUD) patients were compared with 34 age/sex/body mass index-matched controls. Concentrations of total LPA and 16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA species were quantified and correlated with neuroplasticity-associated growth factors including brain derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-2, and neurotrophin-3 (NT-3). AUD patients showed dysexecutive syndrome (22.4%) and memory impairment (32.6%). Total LPA, 16:0-LPA, 18:0-LPA and 18:1-LPA concentrations, were decreased in the AUD group compared to control group. Total LPA, 16:0-LPA, 18:2-LPA and 20:4-LPA concentrations were decreased in men compared to women. Frontal lobe functions correlated with plasma LPA species. Alcohol-cognitive impairments could be related with the deregulation of the LPA species, especially in 16:0-LPA, 18:1-LPA and 20:4-LPA. Concentrations of BDNF correlated with total LPA, 18:2-LPA and 20:4-LPA species. The relation between LPA species and BDNF is interesting in plasticity and neurogenesis functions, their involvement in AUD might serve as a biomarker of cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

García-Marchena

Pizarro

Pavón

et al. 2020

Sci Rep

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“…The latter then acts as the substrate for producing LPA by a dual-function ectoenzyme named autotaxin (ATX), while AA is further converted to pro-inflammatory mediators. ATX, also known as the ectonucleotide pyrophosphatase/phosphodiesterase-2 (ENPP2), is a soluble enzyme mainly found in plasma and cerebrospinal fluid (CSF; Herr et al, 2020). Aberrant ATX expression and malfunction in the autotaxin-LPA (ATX-LPA) axis have been suggested to promote the initiation and progression of AD pathology (Ramesh et al, 2018;Herr et al, 2020).…”

Section: Metabolism Of Cellular Lpa and S1pmentioning

confidence: 99%

“…ATX, also known as the ectonucleotide pyrophosphatase/phosphodiesterase-2 (ENPP2), is a soluble enzyme mainly found in plasma and cerebrospinal fluid (CSF; Herr et al, 2020). Aberrant ATX expression and malfunction in the autotaxin-LPA (ATX-LPA) axis have been suggested to promote the initiation and progression of AD pathology (Ramesh et al, 2018;Herr et al, 2020). S1P Metabolism S1P levels in human tissues are under sophisticated regulation with two bioactive enzymes; sphingosine kinase (SphK), which is related to S1P biosynthesis, and sphingosine-1-phosphate lyase (SPL), which governs S1P degradation.…”

Section: Metabolism Of Cellular Lpa and S1pmentioning

confidence: 99%

Lysophospholipids and Their G-Coupled Protein Signaling in Alzheimer’s Disease: From Physiological Performance to Pathological Impairment

Hao

Guo

Feng

et al. 2020

Front. Mol. Neurosci.

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Lysophospholipids (LPLs) are bioactive signaling lipids that are generated from phospholipase-mediated hydrolyzation of membrane phospholipids (PLs) and sphingolipids (SLs). Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are two of the best-characterized LPLs which mediate a variety of cellular physiological responses via specific G-protein coupled receptor (GPCR) mediated signaling pathways. Considerable evidence now demonstrates the crucial role of LPA and S1P in neurodegenerative diseases, especially in Alzheimer's disease (AD). Dysfunction of LPA and S1P metabolism can lead to aberrant accumulation of amyloid-β (Aβ) peptides, the formation of neurofibrillary tangles (NFTs), neuroinflammation and ultimately neuronal death. Summarizing LPA and S1P signaling profile may aid in profound health and pathological processes. In the current review, we will introduce the metabolism as well as the physiological roles of LPA and S1P in maintaining the normal functions of the nervous system. Given these pivotal functions, we will further discuss the role of dysregulation of LPA and S1P in promoting AD pathogenesis.

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“…In hepatic encephalopathy mice, elevated serum ATX activates the LPA6-associated Gα12/13-Rho pathway in cerebral capillary vessel endothelial cells, resulting in enhanced blood-brain barrier (BBB) permeability and brain edema. The role of the LPA6 receptor in hepatic encephalopathy is suggested [100,101]. In addition, LPA and the tricyclic antidepressant amitriptyline (TCA) signaled LPAR1 to cut down P-glycoprotein transport in the BBB, thereby increasing drug delivery in blood-brain therapy [102].…”

Section: Lpar and Hepatic Encephalopathymentioning

confidence: 99%

“…It suggests that LPA has neuroprotective effects on the retina by binding to different LPA receptors on different cells, or has a neurodegenerative effect [104]. LPAR1 and LPAR2 were also associated with schizophrenia [100,104].…”

Section: Lpar and Retinopathymentioning

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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Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases

Cited by 38 publications

References 186 publications

Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

Lysophospholipids and Their G-Coupled Protein Signaling in Alzheimer’s Disease: From Physiological Performance to Pathological Impairment

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

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