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AC-186, a Selective Nonsteroidal Estrogen Receptor beta Agonist, Shows Gender Specific Neuroprotection in a Parkinson's Disease Rat Model

McFarland, Krista ; Price, Diana L. ; Davis, Christopher N. ; Ma, Jian-Nong ; Bonhaus, Douglas W. ; Burstein, Ethan S. and Olsson, Roger LU (2013) In ACS Chemical Neuroscience 4(9). p.1249-1255
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Parkinson's disease, neuroprotection, AC-186, gender difference, buccal/sublingual administration, selective estrogen receptor beta, agonist
in
ACS Chemical Neuroscience
volume
4
issue
9
pages
1249 - 1255
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000324785800002
  • scopus:84884404963
  • pmid:23898966
ISSN
1948-7193
DOI
10.1021/cn400132u
language
English
LU publication?
yes
id
fa50a982-bbf7-4789-93a1-25c904ce9769 (old id 4172569)
date added to LUP
2016-04-01 14:13:44
date last changed
2020-01-12 15:16:47
@article{fa50a982-bbf7-4789-93a1-25c904ce9769,
  abstract     = {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.},
  author       = {McFarland, Krista and Price, Diana L. and Davis, Christopher N. and Ma, Jian-Nong and Bonhaus, Douglas W. and Burstein, Ethan S. and Olsson, Roger},
  issn         = {1948-7193},
  language     = {eng},
  number       = {9},
  pages        = {1249--1255},
  publisher    = {The American Chemical Society (ACS)},
  series       = {ACS Chemical Neuroscience},
  title        = {AC-186, a Selective Nonsteroidal Estrogen Receptor beta Agonist, Shows Gender Specific Neuroprotection in a Parkinson's Disease Rat Model},
  url          = {http://dx.doi.org/10.1021/cn400132u},
  doi          = {10.1021/cn400132u},
  volume       = {4},
  year         = {2013},
}