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Thyroid Hormone Potentially Benefits Multiple Sclerosis via Facilitating Remyelination

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Abstract

Myelin destruction due to inflammatory damage of oligodendrocytes (OLs) in conjunction with axonal degeneration is one of the major histopathological hallmarks of multiple sclerosis (MS), a common autoimmune disorder affecting the central nervous system (CNS). Therapies over the last 20 years mainly focus on the immune system and, more specifically, on the modulation of immune cell behavior. It seems to be effective in MS with relapse, while it is of little benefit to progressive MS in which neurodegeneration following demyelination outweighs inflammation. Otherwise, remyelination, as a result of oligodendrocyte production from oligodendrocyte precursor cells (OPCs), is considered to be a potential target for the treatment of progressive MS. In this review, positive effects of remyelination on MS will be discussed in view of the critical role played by thyroid hormone (TH), focusing on the following points: (1) promising treatment of TH on MS that potentially targets to remyelination; (2) the active role of TH that is able to promote remyelination; (3) the regulative role of TH that works on endogenous stem and precursor cells; (4) the effect of TH on gene transcription; and (5) a working hypothesis which is developed that TH can alleviate MS by promoting remyelination, and the mechanism of which is its regulative role in gene transcription of OPCs.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

cDNA:

Complementary deoxyribonucleic acid

CNP:

Cyclic nucleotide 3′-phosphodiesterase

CNS:

Central nervous system

CXCL12:

Chemokine (C-X-C motif) ligand 12

CXCR4:

(C-X-C motif) receptor 4

CXCL12/CXCR4:

Chemokine (C-X-C motif) ligand 12/(C-X-C motif) receptor 4

DR-4:

Direct repeat 4

DR-4 TRE:

Thyroid hormone receptor element of direct repeat 4

EAE:

Experimental allergic encephalomyelitis

F2:

Inverted palindrome

FGF-2:

Fibroblast growth factor 2

iPSCs:

Induced pluripotent stem cells

KLF9:

Kruppel-like factor 9

MAG:

Myelin-associated glycoprotein

MBP:

Myelin basic protein

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

mRNA:

Messenger ribonucleic acid

mRNAs:

Messenger ribonucleic acids

NSCs:

Neural stem cells

OLs:

Oligodendrocytes

OPC:

Oligodendrocyte precursor cell

OPCs:

Oligodendrocyte precursor cells

Pal:

Palindromes

PDGF-α:

Platelet-derived growth factor alpha

PLP:

Proteolipid protein

RXR:

Retinoid X receptor

SGZ:

Subgranular zone

SVZ:

Subventricular zone

TH:

Thyroid hormone

TR:

Thyroid hormone receptor

TRE:

Thyroid hormone receptor element

TREs:

Thyroid hormone receptor elements

TRs:

Thyroid hormone receptors

TR-α:

Thyroid hormone alpha receptor

TR-β:

Thyroid hormone beta receptor

V-SVZ:

Ventricular-subventricular zone

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Grant No. 31371147) and the High Education Teaching Reform Project of Chongqing (No. 132080).

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The authors declare that they have no competing interests.

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Zhang, M., Ma, Z., Qin, H. et al. Thyroid Hormone Potentially Benefits Multiple Sclerosis via Facilitating Remyelination. Mol Neurobiol 53, 4406–4416 (2016). https://doi.org/10.1007/s12035-015-9375-z

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  • DOI: https://doi.org/10.1007/s12035-015-9375-z

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