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Quetiapine has an additive effect to triiodothyronine in inducing differentiation of oligodendrocyte precursor cells through induction of cholesterol biosynthesis

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Listed:
  • Jaime Gonzalez Cardona
  • Matthew D Smith
  • Jingya Wang
  • Leslie Kirby
  • Jason T Schott
  • Todd Davidson
  • Jodi L Karnell
  • Katharine A Whartenby
  • Peter A Calabresi

Abstract

Multiple sclerosis (MS) is characterized by demyelinated lesions in the central nervous system. Destruction of myelin and secondary damage to axons and neurons leads to significant disability, particularly in people with progressive MS. Accumulating evidence suggests that the potential for myelin repair exists in MS, although for unclear reasons this process fails. The cells responsible for producing myelin, the oligodendrocytes, and their progenitors, oligodendrocyte precursor cells (OPCs), have been identified at the site of lesions, even in adults. Their presence suggests the possibility that endogenous remyelination without transplantation of donor stem cells may be a mechanism for myelin repair in MS. Strategies to develop novel therapies have focused on induction of signaling pathways that stimulate OPCs to mature into myelin-producing oligodendrocytes that could then possibly remyelinate lesions. We have been investigating pharmacological approaches to enhance OPC differentiation, and have identified that the combination of two agents, triiodothyronine (T3) and quetiapine, leads to an additive effect on OPC differentiation and consequent myelin production via both overlapping and distinct signaling pathways. While the ultimate production of myelin requires cholesterol biosynthesis, we identified that quetiapine enhances gene expression in this pathway more potently than T3. Two blockers of cholesterol production, betulin and simvastatin, reduced OPC differentiation into myelin producing oligodendrocytes. Elucidating the nature of agents that lead to complementary and additive effects on oligodendrocyte differentiation and myelin production may pave the way for more efficient induction of remyelination in people with MS.

Suggested Citation

  • Jaime Gonzalez Cardona & Matthew D Smith & Jingya Wang & Leslie Kirby & Jason T Schott & Todd Davidson & Jodi L Karnell & Katharine A Whartenby & Peter A Calabresi, 2019. "Quetiapine has an additive effect to triiodothyronine in inducing differentiation of oligodendrocyte precursor cells through induction of cholesterol biosynthesis," PLOS ONE, Public Library of Science, vol. 14(9), pages 1-19, September.
  • Handle: RePEc:plo:pone00:0221747
    DOI: 10.1371/journal.pone.0221747
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    1. Friedemann Paul & Sonia Waiczies & Jens Wuerfel & Judith Bellmann-Strobl & Jan Dörr & Helmar Waiczies & Mareile Haertle & Klaus D Wernecke & Hans-Dieter Volk & Orhan Aktas & Frauke Zipp, 2008. "Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis," PLOS ONE, Public Library of Science, vol. 3(4), pages 1-9, April.
    2. Fadi J. Najm & Mayur Madhavan & Anita Zaremba & Elizabeth Shick & Robert T. Karl & Daniel C. Factor & Tyler E. Miller & Zachary S. Nevin & Christopher Kantor & Alex Sargent & Kevin L. Quick & Daniela , 2015. "Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo," Nature, Nature, vol. 522(7555), pages 216-220, June.
    3. Vishal A. Deshmukh & Virginie Tardif & Costas A. Lyssiotis & Chelsea C. Green & Bilal Kerman & Hyung Joon Kim & Krishnan Padmanabhan & Jonathan G. Swoboda & Insha Ahmad & Toru Kondo & Fred H. Gage & A, 2013. "A regenerative approach to the treatment of multiple sclerosis," Nature, Nature, vol. 502(7471), pages 327-332, October.
    4. Sawsan Youssef & Olaf Stüve & Juan C. Patarroyo & Pedro J. Ruiz & Jennifer L. Radosevich & Eun Mi Hur & Manuel Bravo & Dennis J. Mitchell & Raymond A. Sobel & Lawrence Steinman & Scott S. Zamvil, 2002. "The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease," Nature, Nature, vol. 420(6911), pages 78-84, November.
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