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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4172569
- author
- McFarland, Krista
; Price, Diana L.
; Davis, Christopher N.
; Ma, Jian-Nong
; Bonhaus, Douglas W.
; Burstein, Ethan S.
and Olsson, Roger
LU
- organization
- publishing date
- 2013
- 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
- 2022-02-12 01:28:37
@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}},
keywords = {{Parkinson's disease; neuroprotection; AC-186; gender difference; buccal/sublingual administration; selective estrogen receptor beta; agonist}},
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}},
}