ADP-ribosyl cyclase as a therapeutic target for central nervous system diseases

Alla B. Salmina, Raissa Ya Olovyannikova, Mami Noda, Haruhiro Higashida

研究成果: ジャーナルへの寄稿総説査読

7 被引用数 (Scopus)


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.

ジャーナルCentral Nervous System Agents in Medicinal Chemistry
出版ステータス出版済み - 2006

!!!All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 神経心理学および生理心理学
  • 分子医療


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