Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases. 3136 25

A convergence between molecular biological technique and the technology of miniaturization has produced the "gene chip" or microhybridization array. This device multiplies by several thousand fold the power of the northern blot for studying gene expression. Now, it is possible to survey simultaneously a large fraction of all genes in an experimental organism, and within a few years all of the approximately 140,000 human genes will be within reach of the technique. This capability is not only accelerating the rate of research into gene expression and function, it is changing the perspective of inquiry from single genes in isolation to networks of genes operating as a system. Many neurological diseases, from hydrocephalus to schizophrenia, have a genetic component, and individual responses to therapeutic drugs can vary with the genetic background of patients. In neurology and neurobiology, the ability to obtain "gene expression profiles" from nervous tissue promises to illuminate interactions between neuronal genes and the environment, development, disease, aging, and response to drugs and injury.
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PMID:Gene Chips: Applications to Neuroscience. 3154 85

The aquaporins (AQP), a protein family, were first discovered in the early 1990s. The primary role of aquaporins is to facilitate water transport across multiple cell types. In the spinal cord and brain responsible for most of the water diffusion are AQP4 and AQP1. In this paper, we describe the structure, localization and role of this water channel family, especially AQP4 and AQP1. AQP4 is involved in various pathologies such as: stroke, brain tumors, Neuromyelitis optica (NMO), Alzheimer's Disease (AD), traumatic brain injury, Parkinson's Disease, hydrocephalus, schizophrenia, epilepsy, major depressive disorder, autism. Brain edema is the most important acute complication of the hypoxic-ischemic and it has no pathogenic treatment. Imaging and histopathology studies have shown that inhibition of AQP4 reduces brain edema.
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PMID:Distribution of Aquaporins 1 and 4 in the Central Nervous System. 3162 51


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