Identify the novel target molecules of valproic acid using model organism

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460339
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kobe University
• Principal Investigator: Yan Ma 神戸大学, 医学部附属病院, 医員 (70457050)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: バルプロ酸 / 分子標的 / 分裂酵母

Outline of Final Research Achievements

Valproic acid (VPA) is widely used as an anticonvulsant drug. More recently, it has been reported that VPA improved the efficiency upon iPS reprogramming and the administration of VPA dramatically enhanced the restoration of hind limb function. The exact target molecules of the various effects of VPA remain unclear. We have developed a genetic approach using S pombe as a model organism. This study led to the following findings. We identified a novel VPA sensitive mutant of vas4-1/vrg4-v4, a mutant allele of the vrg4+ gene encoding S pombe homolog of Golgi GDP-mannose transmembrane transporter, and its mammalian homologue encodes disease responsible gene of cochlear like pelvic dysplasia. We found that Vrg4 localizes to Golgi, and isolated several genes as dosage-dependent suppressors of the VPA-sensitive phenotype of vrg4-v4 mutant. Furthermore we found the expression level of many genes was markedly increased or decreased upon VPA treatment using cap analysis of gene expression.

Free Research Field

分子薬理