Effect of curcumin in a mouse model of Pelizaeus-Merzbacher disease

Li Hua Yu, Toshifumi Morimura, Yurika Numata, Ryoko Yamamoto, Naoko Inoue, Barbara Antalfy, Yu ichi Goto, Kimiko Deguchi, Hitoshi Osaka, Ken Inoue

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

PLP1 amino acid substitutions cause accumulation of misfolded protein and induce endoplasmic reticulum (ER) stress, causing Pelizaeus-Merzbacher disease (PMD), a hypomyelinating disorder of the central nerve system. Currently no effective therapy is available for PMD. Promoted by its curative effects in other genetic disease models caused by similar molecular mechanisms, we tested if curcumin, a dietary compound, can rescue the lethal phenotype of a PMD mouse model (myelin synthesis deficient, msd). Curcumin was administered orally to myelin synthesis deficit (msd) mice at 180mg·kg-1·day-1 from the postnatal day 3. We evaluated general and motor status, changes in myelination and apoptosis of oligodendrocytes by neuropathological and biochemical examination, and transcription levels for ER-related molecules. We also examined the pharmacological effect of curcumin in cell culture system. Oral curcumin treatment resulted in 25% longer survival (p<0.01). In addition, oligodendrocytes undergoing apoptosis were reduced in number (p<0.05). However, no apparent improvement in motor function, neurological phenotype, and myelin formation was observed. Curcumin treatment did not change the expression of ER stress markers and subcellular localization of the mutant protein in vitro and/or in vivo. Curcumin partially mitigated the clinical and pathological phenotype of msd mice, although molecular mechanisms underlying this curative effect are yet undetermined. Nonetheless, curcumin may serve as a potential therapeutic compound for PMD caused by PLP1 point mutations.

Original languageEnglish
Pages (from-to)108-114
Number of pages7
JournalMolecular Genetics and Metabolism
Volume106
Issue number1
DOIs
Publication statusPublished - 2012 May 1
Externally publishedYes

Keywords

  • CNS
  • Food compound
  • Hypomyelinating disease
  • Model mouse
  • Protein misfolding
  • Treatment

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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  • Cite this

    Yu, L. H., Morimura, T., Numata, Y., Yamamoto, R., Inoue, N., Antalfy, B., Goto, Y. I., Deguchi, K., Osaka, H., & Inoue, K. (2012). Effect of curcumin in a mouse model of Pelizaeus-Merzbacher disease. Molecular Genetics and Metabolism, 106(1), 108-114. https://doi.org/10.1016/j.ymgme.2012.02.016