Please use this identifier to cite or link to this item: https://doi.org/10.1007/s12035-019-01719-1
Title: Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases
Authors: Herr, Deron R 
Chew, Wee Siong 
Satish, RL 
Ong, Wei-Yi 
Keywords: Autotaxin
Lysophospholipase D
Inflammatory neuropathic pain
Glioblastoma multiforme
Hemorrhagic hydrocephalus
Schizophrenia
Multiple sclerosis
Alzheimer's disease
Metabolic syndrome-induced brain damage
Traumatic brain injury
Hepatic encephalopathy induced cerebral edema
Macular edema
Major depressive disorder
Stress-induced psychiatric disorder
Alcohol-induced brain damage
HIV-induced brain injury
Pruritus
Peripheral nerve injury
Issue Date: 1-Jan-2020
Publisher: SPRINGER
Citation: Herr, Deron R, Chew, Wee Siong, Satish, RL, Ong, Wei-Yi (2020-01-01). Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases. MOLECULAR NEUROBIOLOGY 57 (1) : 372-392. ScholarBank@NUS Repository. https://doi.org/10.1007/s12035-019-01719-1
Abstract: Autotaxin (ATX) is a soluble extracellular enzyme that is abundant in mammalian plasma and cerebrospinal fluid (CSF). It has two known enzymatic activities, acting as both a phosphodiesterase and a phospholipase. The majority of its biological effects have been associated with its ability to liberate lysophosphatidic acid (LPA) from its substrate, lysophosphatidylcholine (LPC). LPA has diverse pleiotropic effects in the central nervous system (CNS) and other tissues via the activation of a family of six cognate G protein-coupled receptors. These LPA receptors (LPARs) are expressed in some combination in all known cell types in the CNS where they mediate such fundamental cellular processes as proliferation, differentiation, migration, chronic inflammation, and cytoskeletal organization. As a result, dysregulation of LPA content may contribute to many CNS and PNS disorders such as chronic inflammatory or neuropathic pain, glioblastoma multiforme (GBM), hemorrhagic hydrocephalus, schizophrenia, multiple sclerosis, Alzheimer’s disease, metabolic syndrome-induced brain damage, traumatic brain injury, hepatic encephalopathy-induced cerebral edema, macular edema, major depressive disorder, stress-induced psychiatric disorder, alcohol-induced brain damage, HIV-induced brain injury, pruritus, and peripheral nerve injury. ATX activity is now known to be the primary biological source of this bioactive signaling lipid, and as such, represents a potentially high-value drug target. There is currently one ATX inhibitor entering phase III clinical trials, with several additional preclinical compounds under investigation. This review discusses the physiological and pathological significance of the ATX-LPA-LPA receptor signaling axis and summarizes the evidence for targeting this pathway for the treatment of CNS diseases.
Source Title: MOLECULAR NEUROBIOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/219248
ISSN: 0893-7648
1559-1182
DOI: 10.1007/s12035-019-01719-1
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