Journal article
Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice
Brain (London, England : 1878), Vol.135(12), pp.3551-3566
12/2012
DOI: 10.1093/brain/aws299
PMCID: PMC3577101
PMID: 23250879
Abstract
Charcot–Marie–Tooth disease type 1B is caused by mutations in myelin protein zero. R98C mice, an authentic model of early onset Charcot–Marie–Tooth disease type 1B, develop neuropathy in part because the misfolded mutant myelin protein zero is retained in the endoplasmic reticulum where it activates the unfolded protein response. Because oral curcumin, a component of the spice turmeric, has been shown to relieve endoplasmic reticulum stress and decrease the activation of the unfolded protein response, we treated R98C mutant mice with daily gastric lavage of curcumin or curcumin derivatives starting at 4 days of age and analysed them for clinical disability, electrophysiological parameters and peripheral nerve morphology. Heterozygous R98C mice treated with curcumin dissolved in sesame oil or phosphatidylcholine curcumin performed as well as wild-type littermates on a rotarod test and had increased numbers of large-diameter axons in their sciatic nerves. Treatment with the latter two compounds also increased compound muscle action potential amplitudes and the innervation of neuromuscular junctions in both heterozygous and homozygous R98C animals, but it did not improve nerve conduction velocity, myelin thickness, G-ratios or myelin period. The expression of c-Jun and suppressed cAMP-inducible POU (SCIP)—transcription factors that inhibit myelination when overexpressed—was also decreased by treatment. Consistent with its role in reducing endoplasmic reticulum stress, treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin was associated with decreased X-box binding protein (XBP1) splicing. Taken together, these data demonstrate that treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin improves the peripheral neuropathy of R98C mice by alleviating endoplasmic reticulum stress, by reducing the activation of unfolded protein response and by promoting Schwann cell differentiation.
Details
- Title: Subtitle
- Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice
- Creators
- Ágnes Patzkó - Department of Neurology, Wayne State University, Detroit, MI 48201, USAYunhong Bai - Department of Neurology, Wayne State University, Detroit, MI 48201, USAMario A Saporta - Department of Neurology, Wayne State University, Detroit, MI 48201, USAIstván Katona - Department of Neurology, Wayne State University, Detroit, MI 48201, USAXingYao Wu - Department of Neurology, Wayne State University, Detroit, MI 48201, USADomenica Vizzuso - Hunter James Kelly Institute, School of Medicine and Biomedical Sciences, Dept of Neurology and Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USAM. Laura Feltri - Hunter James Kelly Institute, School of Medicine and Biomedical Sciences, Dept of Neurology and Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USASuola Wang - Department of Neurology, Wayne State University, Detroit, MI 48201, USALisa M Dillon - Department of Neurology, Wayne State University, Detroit, MI 48201, USAJohn Kamholz - Department of Neurology, Wayne State University, Detroit, MI 48201, USADaniel Kirschner - Department of Biology, Boston College, Chestnut Hill, MA 02467-3804, USAFazlul H Sarkar - Department of Pathology, Wayne State University, Detroit, MI 48201, USALawrence Wrabetz - Hunter James Kelly Institute, School of Medicine and Biomedical Sciences, Dept of Neurology and Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USAMichael E Shy - Department of Neurology, Wayne State University, Detroit, MI 48201, USA
- Resource Type
- Journal article
- Publication Details
- Brain (London, England : 1878), Vol.135(12), pp.3551-3566
- DOI
- 10.1093/brain/aws299
- PMID
- 23250879
- PMCID
- PMC3577101
- NLM abbreviation
- Brain
- ISSN
- 0006-8950
- eISSN
- 1460-2156
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 12/2012
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020617102771
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