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Abstract Title:

Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice.

Abstract Source:

Brain. 2012 Dec ;135(Pt 12):3551-66. PMID: 23250879

Abstract Author(s):

Agnes Patzkó, Yunhong Bai, Mario A Saporta, István Katona, Xingyao Wu, Domenica Vizzuso, M Laura Feltri, Suola Wang, Lisa M Dillon, John Kamholz, Daniel Kirschner, Fazlul H Sarkar, Lawrence Wrabetz, Michael E Shy

Article Affiliation:

Carver College of Medicine, University of Iowa, 200 Hawkins Drive, 1188 Medical Laboratories, Iowa City, IA 52242, USA.

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.

Study Type : Animal Study

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Sayer Ji
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