Format

Send to

Choose Destination
Brain Res Bull. 2014 Oct;109:22-31. doi: 10.1016/j.brainresbull.2014.09.004. Epub 2014 Sep 20.

Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration.

Author information

1
University of South Carolina School of Medicine, Department of Pathology, Microbiology, and Immunology, Columbia, SC 29209, USA.
2
Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
3
Department of Neurosurgery and Neurology, Medical University of South Carolina, Charleston, SC 29425, USA.
4
University of South Carolina School of Medicine, Department of Pathology, Microbiology, and Immunology, Columbia, SC 29209, USA. Electronic address: swapan.ray@uscmed.sc.edu.

Abstract

Recent results from laboratory investigations and clinical trials indicate important roles for estrogen receptor (ER) agonists in protecting the central nervous system (CNS) from noxious consequences of neuroinflammation and neurodegeneration. Neurodegenerative processes in several CNS disorders including spinal cord injury (SCI), multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD) are associated with activation of microglia and astrocytes, which drive the resident neuroinflammatory response. During neurodegenerative processes, activated microglia and astrocytes cause deleterious effects on surrounding neurons. The inhibitory activity of ER agonists on microglia activation might be a beneficial therapeutic option for delaying the onset or progression of neurodegenerative injuries and diseases. Recent studies suggest that ER agonists can provide neuroprotection by modulation of cell survival mechanisms, synaptic reorganization, regenerative responses to axonal injury, and neurogenesis process. The anti-inflammatory and neuroprotective actions of ER agonists are mediated mainly via two ERs known as ERα and ERβ. Although some studies have suggested that ER agonists may be deleterious to some neuronal populations, the potential clinical benefits of ER agonists for augmenting cognitive function may triumph over the associated side effects. Also, understanding the modulatory activities of ER agonists on inflammatory pathways will possibly lead to the development of selective anti-inflammatory molecules with neuroprotective roles in different CNS disorders such as SCI, MS, PD, and AD in humans. Future studies should be concentrated on finding the most plausible molecular pathways for enhancing protective functions of ER agonists in treating neuroinflammatory and neurodegenerative injuries and diseases in the CNS.

KEYWORDS:

Estrogen receptor agonists; Inflammation; Neurodisorders; Neuroprotection

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center