33 Citations (Scopus)

Abstract

In the adult nervous system, the major source of nucleotide synthesis is the salvage pathway. Uridine is the major form of pyrimidine nucleosides taken up by the brain. Uridine is phosphorylated to nucleotides, which are used for DNA and RNA synthesis as well as for the synthesis of membrane constituents and glycosylation. Uridine nucleotides and UDP-sugars may be released from neuronal and glial cells. Plasmamembrane receptors of 7 transmembrane domains have been identified that recognize UTP, UDP, and UDP-sugar conjugates. These receptors are called P2Y2 and P2Y4, P2Y6, and P2Y14 receptors, respectively. In addition, binding sites for uridine itself have also been suggested. Furthermore, uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal plasticity. Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role in neuronal functions is not established yet. There is also a scarcity of data regarding the brain distribution of other components of the pyrimidine metabolism although site specific functions exerted by their receptors might require different metabolic support. Despite the gaps in our knowledge on the neuronal functions of pyrimidine nucleosides, their therapeutic utilization is appealing. They have been suggested for the treatment of epileptic and neurodegenerative diseases as neuroprotective agents. In addition, the development of traditional drugs acting specifically on pyrimidine receptor subtypes is also promising as a new direction to treat neurological disorders.

Original languageEnglish
Pages (from-to)1058-1067
Number of pages10
JournalCurrent Topics in Medicinal Chemistry
Volume11
Issue number8
DOIs
Publication statusPublished - 2011

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Uridine
Central Nervous System
Uridine Diphosphate Sugars
Pyrimidine Nucleosides
Brain
Nucleotides
Purinergic P2Y2 Receptors
Uracil Nucleotides
Binding Sites
Uridine Triphosphate
Neuronal Plasticity
Uridine Diphosphate
Neuroprotective Agents
Nervous System Diseases
Glycosylation
Neuroglia
Neurodegenerative Diseases
Nervous System
Sleep
RNA

ASJC Scopus subject areas

  • Drug Discovery

Cite this

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title = "Uridine function in the central nervous system",
abstract = "In the adult nervous system, the major source of nucleotide synthesis is the salvage pathway. Uridine is the major form of pyrimidine nucleosides taken up by the brain. Uridine is phosphorylated to nucleotides, which are used for DNA and RNA synthesis as well as for the synthesis of membrane constituents and glycosylation. Uridine nucleotides and UDP-sugars may be released from neuronal and glial cells. Plasmamembrane receptors of 7 transmembrane domains have been identified that recognize UTP, UDP, and UDP-sugar conjugates. These receptors are called P2Y2 and P2Y4, P2Y6, and P2Y14 receptors, respectively. In addition, binding sites for uridine itself have also been suggested. Furthermore, uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal plasticity. Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role in neuronal functions is not established yet. There is also a scarcity of data regarding the brain distribution of other components of the pyrimidine metabolism although site specific functions exerted by their receptors might require different metabolic support. Despite the gaps in our knowledge on the neuronal functions of pyrimidine nucleosides, their therapeutic utilization is appealing. They have been suggested for the treatment of epileptic and neurodegenerative diseases as neuroprotective agents. In addition, the development of traditional drugs acting specifically on pyrimidine receptor subtypes is also promising as a new direction to treat neurological disorders.",
keywords = "Epilepsy, Neural function, Neuronal plasticity, Nucleoside transport, Nucleotide receptor, Pyrimidine salvage, Sleep, Therapeutic application",
author = "A. Dobolyi and G. Juh{\'a}sz and Z. Kov{\'a}cs and J. Kardos",
year = "2011",
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language = "English",
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pages = "1058--1067",
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T1 - Uridine function in the central nervous system

AU - Dobolyi, A.

AU - Juhász, G.

AU - Kovács, Z.

AU - Kardos, J.

PY - 2011

Y1 - 2011

N2 - In the adult nervous system, the major source of nucleotide synthesis is the salvage pathway. Uridine is the major form of pyrimidine nucleosides taken up by the brain. Uridine is phosphorylated to nucleotides, which are used for DNA and RNA synthesis as well as for the synthesis of membrane constituents and glycosylation. Uridine nucleotides and UDP-sugars may be released from neuronal and glial cells. Plasmamembrane receptors of 7 transmembrane domains have been identified that recognize UTP, UDP, and UDP-sugar conjugates. These receptors are called P2Y2 and P2Y4, P2Y6, and P2Y14 receptors, respectively. In addition, binding sites for uridine itself have also been suggested. Furthermore, uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal plasticity. Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role in neuronal functions is not established yet. There is also a scarcity of data regarding the brain distribution of other components of the pyrimidine metabolism although site specific functions exerted by their receptors might require different metabolic support. Despite the gaps in our knowledge on the neuronal functions of pyrimidine nucleosides, their therapeutic utilization is appealing. They have been suggested for the treatment of epileptic and neurodegenerative diseases as neuroprotective agents. In addition, the development of traditional drugs acting specifically on pyrimidine receptor subtypes is also promising as a new direction to treat neurological disorders.

AB - In the adult nervous system, the major source of nucleotide synthesis is the salvage pathway. Uridine is the major form of pyrimidine nucleosides taken up by the brain. Uridine is phosphorylated to nucleotides, which are used for DNA and RNA synthesis as well as for the synthesis of membrane constituents and glycosylation. Uridine nucleotides and UDP-sugars may be released from neuronal and glial cells. Plasmamembrane receptors of 7 transmembrane domains have been identified that recognize UTP, UDP, and UDP-sugar conjugates. These receptors are called P2Y2 and P2Y4, P2Y6, and P2Y14 receptors, respectively. In addition, binding sites for uridine itself have also been suggested. Furthermore, uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal plasticity. Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role in neuronal functions is not established yet. There is also a scarcity of data regarding the brain distribution of other components of the pyrimidine metabolism although site specific functions exerted by their receptors might require different metabolic support. Despite the gaps in our knowledge on the neuronal functions of pyrimidine nucleosides, their therapeutic utilization is appealing. They have been suggested for the treatment of epileptic and neurodegenerative diseases as neuroprotective agents. In addition, the development of traditional drugs acting specifically on pyrimidine receptor subtypes is also promising as a new direction to treat neurological disorders.

KW - Epilepsy

KW - Neural function

KW - Neuronal plasticity

KW - Nucleoside transport

KW - Nucleotide receptor

KW - Pyrimidine salvage

KW - Sleep

KW - Therapeutic application

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