Abstract
Drugs that selectively activate estrogen receptor β (ERβ) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ERβ and ERα. The selective ERβ agonist AC-186 was evaluated in a rat model of Parkinson's disease induced through bilateral 6-hydroxydopamine lesions of the substantia nigra. In this model, AC-186 prevented motor, cognitive, and sensorimotor gating deficits and mitigated the loss of dopamine neurons in the substantia nigra, in males, but not in females. Furthermore, in male rats, 17β-estradiol, which activates ERβ and ERα with equal potency, did not show the same neuroprotective benefits as AC-186. Hence, in addition to a beneficial safety profile for use in both males and females, a selective ERβ agonist has a differentiated pharmacological profile compared to 17β-estradiol in males.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Corpus Striatum / chemistry
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Corpus Striatum / drug effects
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Corpus Striatum / pathology
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Cyclohexanes / chemistry
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Cyclohexanes / pharmacology
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Cyclohexanes / therapeutic use*
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Cytokines / analysis
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Drug Evaluation, Preclinical
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Estradiol / therapeutic use
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Estrogen Receptor beta / agonists*
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Exploratory Behavior / drug effects
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Female
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Male
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Molecular Structure
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Nerve Tissue Proteins / analysis
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology
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Neuroprotective Agents / therapeutic use*
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Ovariectomy
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Oxidopamine / toxicity
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Parkinsonian Disorders / chemically induced
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Parkinsonian Disorders / drug therapy*
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Phenols / chemistry
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Phenols / pharmacology
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Phenols / therapeutic use*
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Rats
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Rats, Sprague-Dawley
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Reflex, Startle / drug effects
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Rotarod Performance Test
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Sex Factors
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Substantia Nigra / chemistry
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Substantia Nigra / drug effects
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Substantia Nigra / pathology
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Tyrosine 3-Monooxygenase / analysis
Substances
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AC-186
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Cyclohexanes
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Cytokines
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Estrogen Receptor beta
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Nerve Tissue Proteins
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Neuroprotective Agents
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Phenols
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Estradiol
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Oxidopamine
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Tyrosine 3-Monooxygenase