Bedside to bench to bedside research: Estrogen receptor beta ligand as a candidate neuroprotective treatment for multiple sclerosis
Noriko Itoh, Roy Kim, Mavis Peng, Emma DiFilippo, Hadley Johnsonbaugh, Allan MacKenzie-Graham, Rhonda R Voskuhl, Noriko Itoh, Roy Kim, Mavis Peng, Emma DiFilippo, Hadley Johnsonbaugh, Allan MacKenzie-Graham, Rhonda R Voskuhl
Abstract
Protective effects of pregnancy during MS have led to clinical trials of estriol, the pregnancy estrogen, in MS. Since estriol binds to estrogen receptor (ER) beta, ER beta ligand could represent a "next generation estriol" treatment. Here, ER beta ligand treatment was protective in EAE in both sexes and across genetic backgrounds. Neuroprotection was shown in spinal cord, sparing myelin and axons, and in brain, sparing neurons and synapses. Longitudinal in vivo MRIs showed decreased brain atrophy in cerebral cortex gray matter and cerebellum during EAE. Investigation of ER beta ligand as a neuroprotective treatment for MS is warranted.
Keywords: Estrogen; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Neuroprotection; Pregnancy.
Copyright © 2016 Elsevier B.V. All rights reserved.
Figures
![Figure 1. Protective effects of ER beta…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5806698/bin/nihms-824541-f0001.jpg)
Figure 2. Whole brain, cerebral cortical and…
Figure 2. Whole brain, cerebral cortical and cerebellar atrophy in EAE are reduced by ER…
Figure 3. ER beta ligand treatment of…
Figure 3. ER beta ligand treatment of EAE: protective effects in cerebral cortical gray matter
Figure 4. ER beta ligand treatment of…
Figure 4. ER beta ligand treatment of EAE: protective effects in cerebellar white and gray…
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- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Animals
- Cyclohexanes / administration & dosage*
- Cyclohexanes / metabolism*
- Estrogen Receptor beta / metabolism*
- Female
- Ligands
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Inbred NOD
- Multiple Sclerosis / metabolism*
- Multiple Sclerosis / prevention & control
- Neuroprotective Agents / administration & dosage*
- Neuroprotective Agents / metabolism*
- Phenols / administration & dosage*
- Phenols / metabolism*
- Treatment Outcome
- AC-186
- Cyclohexanes
- Estrogen Receptor beta
- Ligands
- Neuroprotective Agents
- Phenols
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 2. Whole brain, cerebral cortical and…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5806698/bin/nihms-824541-f0002.jpg)
![Figure 3. ER beta ligand treatment of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5806698/bin/nihms-824541-f0003.jpg)
![Figure 4. ER beta ligand treatment of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5806698/bin/nihms-824541-f0004.jpg)
Source: PubMed