Dataset Information

AC-186, a selective nonsteroidal estrogen receptor ? agonist, shows gender specific neuroprotection in a Parkinson's disease rat model.

ABSTRACT: Drugs that selectively activate estrogen receptor ? (ER?) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ER? and ER?. The selective ER? 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?-estradiol, which activates ER? and ER? 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? agonist has a differentiated pharmacological profile compared to 17?-estradiol in males.

SUBMITTER: McFarland K

PROVIDER: S-EPMC3778431 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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AC-186, a selective nonsteroidal estrogen receptor β agonist, shows gender specific neuroprotection in a Parkinson's disease rat model.

McFarland Krista K Price Diana L DL Davis Christopher N CN Ma Jian-Nong JN Bonhaus Douglas W DW Burstein Ethan S ES Olsson Roger R

ACS chemical neuroscience 20130806 9

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 ...[more]

PMID: 23898966

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Project description:BackgroundThe penetrance of leucine rich repeat kinase 2 (LRRK2) mutations is incomplete and may be influenced by environmental and/or other genetic factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to reduce inflammation and may lower Parkinson's disease (PD) risk, but their role in LRRK2-associated PD is unknown.ObjectivesThe objective of this study is to evaluate the association of regular NSAID use and LRRK2-associated PD.MethodsSymptomatic ("LRRK2-PD") and asymptomatic ("LRRK2-non-PD") participants with LRRK2 G2019S, R1441X, or I2020T variants (definitely pathogenic variant carriers) or G2385R or R1628P variants (risk variant carriers) from 2 international cohorts provided information on regular ibuprofen and/or aspirin use (≥2 pills/week for ≥6 months) prior to the index date (diagnosis date for PD, interview date for non-PD). Multivariate logistic regression was used to evaluate the relationship between regular NSAID use and PD for any NSAID, separately for ibuprofen and aspirin in all carriers and separately in pathogenic and risk variant groups.ResultsA total of 259 LRRK2-PD and 318 LRRK2-non-PD participants were enrolled. Regular NSAID use was associated with reduced odds of PD in the overall cohort (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.21-0.57) and in both pathogenic and risk variant carriers (ORPathogenic , 0.38; 95% CI, 0.21-0.67 and ORRiskVariant , 0.19; 95% CI, 0.04-0.99). Similar associations were observed for ibuprofen and aspirin separately (ORIbuprofen , 0.19; 95% CI, 0.07-0.50 and ORAspirin , 0.51; 95% CI, 0.28-0.91).ConclusionsRegular NSAID use may be associated with reduced penetrance in LRRK2-associated PD. The LRRK2 protein is involved in inflammatory pathways and appears to be modulated by regular anti-inflammatory use. Longitudinal observational and interventional studies of NSAID exposure and LRRK2-PD are needed to confirm this association. © 2020 International Parkinson and Movement Disorder Society.

Dataset Information

AC-186, a selective nonsteroidal estrogen receptor ? agonist, shows gender specific neuroprotection in a Parkinson's disease rat model.

Publications

AC-186, a selective nonsteroidal estrogen receptor β agonist, shows gender specific neuroprotection in a Parkinson's disease rat model.

Similar Datasets

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