title: Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration.
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.
authors.affiliation: University of South Carolina School of Medicine, Department of Pathology, Microbiology, and Immunology, Columbia, SC 29209, USA.
authors.forename: Mrinmay
authors.initials: M
authors.lastname: Chakrabarti
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Azizul
authors.initials: A
authors.lastname: Haque
authors.affiliation: Department of Neurosurgery and Neurology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
authors.affiliation: University of South Carolina School of Medicine, Department of Pathology, Microbiology, and Immunology, Columbia, SC 29209, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Nagarkatti
authors.affiliation: University of South Carolina School of Medicine, Department of Pathology, Microbiology, and Immunology, Columbia, SC 29209, USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.affiliation: University of South Carolina School of Medicine, Department of Pathology, Microbiology, and Immunology, Columbia, SC 29209, USA. Electronic address: swapan.ray@uscmed.sc.edu.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ray
mesh_terms: D000818:Animals; D004660:Encephalitis / Q000188:drug therapy*; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004967:Estrogens; D018696:Neuroprotective Agents
keywords: Estrogen receptor agonists; Inflammation; Neurodisorders; Neuroprotection