GPER: A new tool to protect dopaminergic neurons?
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2015-10-01; 1852(10): 2035-2041
DOI: 10.1016/j.bbadis.2015.07.004
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1. Biochim Biophys Acta. 2015 Oct;1852(10 Pt A):2035-41. doi:
10.1016/j.bbadis.2015.07.004. Epub 2015 Jul 11.
GPER: A new tool to protect dopaminergic neurons?
Bessa A(1), Campos FL(2), Videira RA(3), Mendes-Oliveira J(4), Bessa-Neto D(5),
Baltazar G(6).
Author information:
(1)CICS-UBI – Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal. Electronic address: .
(2)CICS-UBI – Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal. Electronic address: .
(3)CICS-UBI – Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal. Electronic address: .
(4)CICS-UBI – Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal. Electronic address: .
(5)CICS-UBI – Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal. Electronic address: .
(6)CICS-UBI – Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal. Electronic address: .
Parkinson’s disease (PD) is characterized by a selective degeneration of
nigrostriatal dopaminergic pathway. Epidemiological studies revealed a male
predominance of the disease that has been attributed to the female steroid
hormones, mainly the estrogen. Estrogen neuroprotective effects have been shown
in several studies, however the mechanisms responsible by these effects are still
unclear. Previous data from our group revealed that glial cell line-derived
neurotrophic factor (GDNF) is crucial to the dopaminergic protection provided by
17β-estradiol, and also suggest that the intracellular estrogen receptors (ERs)
are not required for that neuroprotective effects. The present study aimed to
investigate the contribution of the G protein-coupled ER (GPER) activation in
estrogen-mediated dopaminergic neuroprotection against an insult induced by
1-methyl-4-phenylpyridinium (MPP(+)), and whether GPER neuroprotective effects
involve the regulation of GDNF expression. Using primary mesencephalic cultures,
we found that GPER activation protects dopaminergic neurons from MPP(+) toxicity
in an extent similar to the promoted by a 17β-estradiol. Moreover, GPER
activation promotes an increase in GDNF levels. Both, GDNF antibody
neutralization or RNA interference-mediated GDNF knockdown prevented the
GPER-mediated dopaminergic protection verified in mesencephalic cultures
challenged with MPP(+). Overall, these results revealed that G1, a selective
agonist of GPER, is able to protect dopaminergic neurons and that GDNF
overexpression is a key feature to GPER induced the neuroprotective effects.
Copyright © 2015 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.bbadis.2015.07.004
PMID: 26170064