TY - JOUR
T1 - ADP-ribosyl cyclase as a therapeutic target for central nervous system diseases
AU - Salmina, Alla B.
AU - Olovyannikova, Raissa Ya
AU - Noda, Mami
AU - Higashida, Haruhiro
PY - 2006
Y1 - 2006
N2 - NAD+ is as abundant as ATP in neuronal cells. NAD+ functions not only as a coenzyme but also as a substrate. NAD+ metabolism in neuronal cells is tightly controlled under physiological conditions, since NAD+ has a great impact on functional activity of neurons upon stimulation. NAD+-utilizing enzymes is involved in signal transduction. We focus on ADP-ribosyl cyclase/CD38 which synthesizes cyclic ADP-ribose (cADPR), a Ca2+ mobilizing messenger. Structural analysis defined the active site of the enzyme. ADP-ribosyl cyclase associated with CD38 was detected in the central nervous system (CNS) where its activity and expression were developmentally regulated. CD38 has been reported to have different subcellular locations either in neurons or in glial cells, suggesting multiple roles. cADPR, acts as a universal calcium mobilizer from intracellular stores independently from inositol trisphosphate which acts through activation/modulation of ryanodine receptor channels involving FKBP12.6. cADPR was also involved in the regulation of some potassium currents in synaptic activity. cADPR synthesis in neuronal cells is stimulated or modulated via different pathways and various factors. Subtype-specific coupling of various neurotransmitter receptors with ADP-ribosyl cyclase confirms the involvement of the enzyme in signal transduction in neurons and glial cells. Therefore, it is possible that pharmacological manipulation of intracellular cADPR levels through ADP-ribosyl cyclase activity or expression, in the CNS may provide new therapeutic opportunities for treatment of neurological disorders.
AB - NAD+ is as abundant as ATP in neuronal cells. NAD+ functions not only as a coenzyme but also as a substrate. NAD+ metabolism in neuronal cells is tightly controlled under physiological conditions, since NAD+ has a great impact on functional activity of neurons upon stimulation. NAD+-utilizing enzymes is involved in signal transduction. We focus on ADP-ribosyl cyclase/CD38 which synthesizes cyclic ADP-ribose (cADPR), a Ca2+ mobilizing messenger. Structural analysis defined the active site of the enzyme. ADP-ribosyl cyclase associated with CD38 was detected in the central nervous system (CNS) where its activity and expression were developmentally regulated. CD38 has been reported to have different subcellular locations either in neurons or in glial cells, suggesting multiple roles. cADPR, acts as a universal calcium mobilizer from intracellular stores independently from inositol trisphosphate which acts through activation/modulation of ryanodine receptor channels involving FKBP12.6. cADPR was also involved in the regulation of some potassium currents in synaptic activity. cADPR synthesis in neuronal cells is stimulated or modulated via different pathways and various factors. Subtype-specific coupling of various neurotransmitter receptors with ADP-ribosyl cyclase confirms the involvement of the enzyme in signal transduction in neurons and glial cells. Therefore, it is possible that pharmacological manipulation of intracellular cADPR levels through ADP-ribosyl cyclase activity or expression, in the CNS may provide new therapeutic opportunities for treatment of neurological disorders.
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U2 - 10.2174/187152406778226699
DO - 10.2174/187152406778226699
M3 - Review article
AN - SCOPUS:33749244616
VL - 6
SP - 193
EP - 210
JO - Central Nervous System Agents in Medicinal Chemistry
JF - Central Nervous System Agents in Medicinal Chemistry
SN - 1871-5249
IS - 3
ER -