AC-186, a Selective Nonsteroidal Estrogen Receptor β Agonist, Shows Gender Specific Neuroprotection in a Parkinson's Disease Rat Model
AC-186, a Selective Nonsteroidal Estrogen Receptor β Agonist, Shows Gender Specific Neuroprotection in a Parkinson's Disease Rat Model
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DOI：
10.1021/cn400132u
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发表时间：
2013-09-01
影响因子：
5
通讯作者：
Olsson, Roger
中科院分区：
文献类型：
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作者：
McFarland, Krista;Price, Diana L.;Olsson, Roger
选择性激活雌激素受体β（ER β）的药物可能比目前用于激活ER β和ER α的激素替代治疗的非选择性雌激素更安全。在通过双侧黑质6-羟基多巴胺损伤诱导的帕金森病大鼠模型中评价了选择性ER β激动剂AC-186。在该模型中，AC-186可预防雄性动物的运动、认知和感觉运动门控缺陷，并减轻黑质中多巴胺神经元的丢失，但在雌性动物中无此作用。此外，在雄性大鼠中，17 β-雌二醇（以同等效力激活ER β和ER α）未显示出与AC-186相同的神经保护益处。因此，除了在男性和女性中使用的有益安全性特征之外，与17 β-雌二醇相比，选择性ER β激动剂在男性中具有不同的药理学特征。
Drugs that selectively activate estrogen receptor beta (ER beta) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ER beta and ER alpha. The selective ER beta 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, 17 beta-estradiol, which activates ER beta and ER alpha 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 ER beta agonist has a differentiated pharmacological profile compared to 17 beta-estradiol in males.